Separation columns and methods for manufacturing the improved separation columns

• US 6,596,144 B1
• Filed: 10/30/2000
• Issued: 07/22/2003
• Est. Priority Date: 05/27/1997
• Status: Expired due to Fees

• Current Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Original Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Inventors: He, Bing, Regnier, Fred E.
• Primary Examiner(s): Nguyen, Nam
• Assistant Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US09/699,674
• Time in Patent Office: 995 Days
• Field of Search: 422/70, 422/99, 204/600, 204/601, 209/128, 209/158
• US Class Current: 204/601
• CPC Class Codes: B01J 20/281 Sorbents specially adapted for preparative, analytical or investigative chromatography
• CPC Class Codes: B01J 2220/54 Sorbents specially adapted for analytical or investigative chromatography
• CPC Class Codes: G01N 2030/0035 electrical field
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 30/02 Column chromatography
• CPC Class Codes: G01N 30/16 Injection G01N30/24 takes precedence
• CPC Class Codes: G01N 30/466 with separation columns in parallel
• CPC Class Codes: G01N 30/60 Construction of the column
• CPC Class Codes: G01N 30/6017 Fluid distributors
• CPC Class Codes: G01N 30/6043 in parallel
• CPC Class Codes: G01N 30/6095 Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: Y10S 366/03 Micromixers: variable geometry from the pathway influences mixing/agitation of non-laminar fluid flow

Abstract

A separation column for use in a separation process such as chromatography, electrochromatography and electrophoresis is described. The separation column includes multiple collocated monolith support structures and interconnected channels defined by the support structures. The monolith support structures and interconnected channels are created on a substrate using an isotropic etching. The separation column also includes a cover plate disposed on the etched surface of the substrate, creating an enclosed separation column.

Claims

1. A separation device having a longitudinal axis, the separation device comprising:

(a) a substrate;

(b) a plurality of collocated monolith support structures, each having a first end, a second end, and a wall therebetween,

 

wherein

the first end of each collocated monolith support structure is congruent with or in contact with the substrate, and

the plurality of collocated monolith support structures are dimensioned and oriented in a uniform two-dimensional array defining a plurality of interconnected channels bound by the walls of the collocated monolith support structures and a surface of the substrate,

wherein the plurality of interconnected channels are non-contiguous across two adjacent collocated monolith support structures in a direction perpendicular to the longitudinal axis of the separation device; and

(c) a channel network, the channel network comprising a plurality of monolith structures, each monolith structure having a first end, a second end, and a wall therebetween,

 

wherein

the first end of each monolith structure is congruent with or in contact with the substrate,

the plurality of monolith structures are dimensioned and oriented to define a second set of interconnected channels which are in fluid communication with the uniform two-dimensional array of interconnected channels, and

the number of interconnected channels in the second set of interconnected channels counted in a direction perpendicular to the longitudinal axis of the separation device comprises less than the number of interconnected channels in the uniform two-dimensional array of interconnected channels by a factor of X, where X is the number of adjacent interconnected channels of the uniform two-dimensional array of interconnected channels which combine into a single channel within the second set of interconnected channels.

2. The separation device of claim 1 wherein the second end of each collocated monolith support structure has a cross-sectional shape wherein the upstream-most point is a vertex.

3. The separation device of claim 1 wherein the second end of each collocated monolith support structure has a cross-sectional shape that is selected from the group consisting of a hexagonal cross section, a tetragonal cross-section, and a dodecagonal, cross-section.

4. The separation device of claim 3 wherein a maximum dimension of the hexagonal cross section is in the direction of the longitudinal axis of the separation device.

5. The separation device of claim 1 wherein at least the walls of the collocated monolith support structures comprise a coating.

6. The separation device of claim 5 wherein the coating comprises moieties selected from the group consisting of cationic groups, anionic groups, hydrocarbon groups, chelation groups, antibodies, antigens, and combinations thereof.

7. The separation device of claim 1 wherein the substrate comprises an electrical connector for electrical communication with an electrical source.

8. The separation device of claim 1 wherein X is two.

9. The separation device of claim 1 wherein the number of interconnected channels in the second set of interconnected channels counted in the direction perpendicular to the longitudinal axis of the separation device decreases by Xⁿ, where n is the number of times the interconnected channels of the second set of interconnected channels combine along a direction of the longitudinal axis of the separation device.

10. The separation device of claim 9 wherein the number of interconnected channels in the second set of interconnected channels counted in the direction perpendicular to the longitudinal axis of the separation device becomes one.

11. The separation device of claim 1 further comprising:

(d) a second channel network in fluid communication with the uniform two-dimensional array of interconnected channels.

12. The separation device of claim 11 wherein X is two.

13. The separation device of claim 11 further comprising a cover plate associated with the second ends of the collocated monolith support structures and the second ends of the monolith structures of the channel network.

14. A method of making the separation device of claim 13 comprising the steps of:

etching the substrate to create the plurality of collocated monolith support structures and the plurality of monolith structures of the channel network; and

associating the cover plate with the second ends of the collocated monolith support structures and the second ends of the monolith structures of the channel network.

15. A separation system comprising:

the separation device of claim 13; and

an electrophoresis apparatus in electrical communication with the separation device.

16. The separation system of claim 15 further comprising a detector in communication with the separation device.

17. The separation system of claim 16 wherein the detector comprises a mass spectrometer.

18. The separation device of claim 11 further comprising:

(e) a third channel network in fluid communication with the uniform two-dimensional array of interconnected channels; and

(f) a fourth channel network in fluid communication with the uniform two-dimensional array of interconnected channels,

wherein the channel network, the second channel network, and the third channel network are adapted to define inlets to the uniform two-dimensional array of interconnected channels, and the fourth channel network is adapted to define an outlet from the two-dimensional array of interconnected channels.

19. A method of making the separation device of claim 1 comprising the step of:

etching the substrate to create the plurality of collocated monolith support structures and the plurality of monolith structures of the channel network.

20. A separation device having a longitudinal axis of bulk liquid flow, the separation device comprising:

(a) a substrate;

(b) a plurality of collocated monolith support structures, each having a first end, a second end, and a wall therebetween,

 

wherein

the first end of each collocated monolith support structure is congruent with or in contact with the substrate,

the plurality of collocated monolith support structures are dimensioned and oriented in a uniform two-dimensional array defining a plurality of interconnected channels bound by the walls of the collocated monolith support structures and a surface of the substrate,

wherein the plurality of interconnected channels are non-contiguous across two adjacent collocated monolith support structures in a direction perpendicular to the longitudinal axis of the separation device;

(c) a channel network, the channel network comprising a plurality of monolith structures, each monolith structure having a first end, a second end, and a wall therebetween,

 

wherein

the first end of each monolith structure is congruent with or in contact with the substrate,

the plurality of monolith structures are dimensioned and oriented to define a second set of interconnected channels which are in fluid communication with the uniform two-dimensional array of interconnected channels, and

the number of interconnected channels in the second set of interconnected channels counted in a direction perpendicular to the longitudinal axis of the separation device comprises less than the number of interconnected channels in the uniform two-dimensional array of interconnected channels by a factor of 2;

(d) a second channel network in fluid communication with the uniform two-dimensional array of interconnected channels; and

(e) a cover plate associated with the second ends of the collocated monolith support structures and the second ends of the monolith structures,

 

wherein

the cover plate comprises a surface in fluid communication with the uniform two-dimensional array of interconnected channels, the second set of interconnected channels of the channel network, and the interconnected channels of the second channel network.

21. The separation device of claim 20 wherein at least the walls of the collocated monolith support structures, the surface of the substrate, and the surface of the cover plate comprise a coating.

22. The separation device of claim 21 wherein the coating comprises moieties selected from the group consisting of cationic groups, anionic groups, hydrocarbon groups, chelation groups, antibodies, antigens, and combinations thereof.

23. The separation device of claim 20 wherein the number of interconnected channels in the second set of interconnected channels of the channel network counted in the direction perpendicular to the longitudinal axis of the separation device decreases by 2ⁿ, where n is the number of times the interconnected channels of the second set of interconnected channels combine along a direction of the longitudinal axis of the separation device.

24. The separation device of claim 23 wherein the number of interconnected channels in the second set of interconnected channels of the channel network counted in the direction perpendicular to the longitudinal axis of the separation device becomes one.

25. The separation device of claim 23 wherein the second channel network comprises a longitudinal axis and a third set of interconnected channels in fluid communication with the uniform two-dimensional array of interconnected channels, and the number of interconnected channels in the third set of interconnected channels of the second channel network counted in the direction perpendicular to the longitudinal axis of the second channel network of the separation device decreases by 2ⁿ, where n is the number of times the interconnected channels of the third set of interconnected channels of the second channel network combine along a direction of the longitudinal axis of the second channel network of the separation device.

26. The separation device of claim 25 wherein the number of interconnected channels in the third set of interconnected channels of the second channel network counted in the direction perpendicular to the longitudinal axis of the second channel network of the separation device becomes one.

27. A method of making the separation device of claim 20 comprising the steps of:

etching the substrate to create the plurality of collocated monolith support structures, the plurality of monolith support structures of the channel network and of the second channel network; and

associating the cover plate with the second ends of the collocated monolith support structures and the second ends of the monolith structures of the channel network and of the second channel network.

28. A separation system comprising:

the separation device of claim 20; and

an electrophoresis apparatus in electrical communication with the separation device.

29. The separation system of claim 28 further comprising a detector in communication with the separation device.

30. A monolith distributor having a longitudinal axis, the monolith distributor comprising:

a substrate; and

a channel network, the channel network comprising a plurality of monolith structures, each monolith structure having a first end, a second end, and a wall therebetween,

 

wherein

the first end of each monolith structure is congruent with or in contact with the substrate,

the plurality of monolith structures are dimensioned and oriented to define a set of interconnected channels,

 

wherein

the number of interconnected channels in the set of interconnected channels counted in a direction perpendicular to the longitudinal axis of the monolith distributor increases by Xⁿ, where n is the number of times the interconnected channels split along the direction of the longitudinal axis of the monolith distributor and X is the number of interconnected channels into which the preceding interconnected channel splits,

 

wherein

each of the interconnected channels has a cross-sectional area measured in the direction perpendicular to the longitudinal axis of the monolith distributor, and the cross-sectional area of each of the interconnected channels decreases as the number of interconnected channels along the direction of the longitudinal axis of the monolith distributor increases.

31. The monolith distributor of claim 30 wherein X is 2.

32. The monolith distributor of claim 30 wherein the monolith distributor is adapted to be a monolith collector.

33. The monolith distributor of claim 32 wherein the number of interconnected channels in the set of interconnected channels counted in a direction perpendicular to the longitudinal axis of the monolith distributor increases from a single channel by Xⁿ, and the single channel is an outlet from a chromatography column.

34. The monolith distributor of claim 30 further comprising a cover plate associated with the second ends of the monolith structures.

35. The monolith distributor of claim 30 wherein the monolith distributor is adapted for use in a chromatographic application, an electrophoretic application, or an electroosmotic application.

36. The monolith distributor of claim 30 wherein the number of interconnected channels in the set of interconnected channels counted in a direction perpendicular to the longitudinal axis of the monolith distributor increases from a single channel by Xⁿ, and the single channel is an inlet to a chromatography column.