Miniaturized planar columns in novel support media for liquid phase analysis

• US 5,658,413 A
• Filed: 06/07/1995
• Issued: 08/19/1997
• Est. Priority Date: 10/19/1994
• Status: Expired due to Term

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Hewlett-Packard Company (HP Inc.)
• Inventors: Mittelstadt, Laurie S., Bek, Fritz, Swedberg, Sally A., Kaltenbach, Patrick, Witt, Klaus E.
• Primary Examiner(s): Engel, James
• Assistant Examiner(s): Rivard, Paul M.
• Application Number:
  US08/482,245
• Time in Patent Office: 804 Days
• Field of Search: 156/272.8, 156/217, 156/292, 156/290, 73/61.52, 210/198.2, 210/656, 422/70, 95/82, 264/220, 264/328.1, 264/328.2, 264/156
• US Class Current: 156/272.8
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/1822 using Peltier elements
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/5055 Hinged, e.g. opposable surfaces
• CPC Class Codes: B01L 7/54 using spatial temperature gradients
• CPC Class Codes: B29C 65/02 by heating, with or without pressure
• CPC Class Codes: B29C 66/54 Joining several hollow-preforms, e.g. half-shells, to form hollow articles, e.g. for making balls, containers; Joining several hollow-preforms, e.g. half-cylinders, to form tubular articles
• CPC Class Codes: B29C 66/549 said hollow-preforms being interconnected during their moulding process, e.g. by a hinge
• CPC Class Codes: B29L 2031/756 Microarticles, nanoarticles
• CPC Class Codes: G01N 2030/0035 electrical field
• CPC Class Codes: G01N 2030/285 electrically driven carrier
• CPC Class Codes: G01N 2030/3007 : same temperature for whole column
• CPC Class Codes: G01N 2030/3015 : temperature gradients along column
• CPC Class Codes: G01N 2030/303 : using peltier elements
• CPC Class Codes: G01N 27/44704 : Details; Accessories
• CPC Class Codes: G01N 27/44708 : Cooling
• CPC Class Codes: G01N 27/44721 : by optical means
• CPC Class Codes: G01N 27/44773 : Multi-stage electrophoresis, e.g. two-dimensional electrophoresis
• 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 30/60 : Construction of the column
• CPC Class Codes: G01N 30/6047 : with supporting means; Holders
• CPC Class Codes: G01N 30/6052 : body
• CPC Class Codes: G01N 30/606 : with fluid access or exit ports
• CPC Class Codes: G01N 30/6095 : Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: Y10T 156/1064 : Partial cutting [e.g., grooving or incising]

Abstract

Miniaturized planar column devices are described for use in liquid phase analysis, the devices comprising microstructures fabricated by laser ablation in a variety of novel support substrates. Devices formed according to the invention include associated laser-ablated features required for function, such as analyte detection means and fluid communication means. Miniaturized columns constructed under the invention find use in any analysis system performed on either small and/or macromolecular solutes in the liquid phase and may employ chromatographic, electrophoretic, electrochromatographic separation means, or any combination thereof.

Claims

1. A miniaturized column device comprising:

a substrate having first and second substantially planar opposing surfaces wherein said substrate is comprised of a material other than silicon or silicon dioxide, said substrate having a microchannel laser-ablated in the first planar surface;

a cover plate arranged over the first planar surface, said cover plate in combination with the microchannel defining an elongate separation compartment; and

at least one inlet port and at least one outlet port communicating with the separation compartment, said ports enabling the passage of fluid from an external source through the separation compartment.

2. The miniaturized column of claim 1, further comprising first detection means laser-ablated in the substrate, wherein said first detection means is in communication with the separation compartment thereby enabling detection of a sample passing through the separation compartment.

3. The miniaturized column of claim 2, wherein the substrate is selected from the group consisting of polymeric materials, ceramic materials, and combinations thereof.

4. The miniaturized column of claim 3 further comprising second detection means laser-ablated in the cover plate, wherein said second detection means is in communication with the separation compartment and positioned opposite the first detection means.

5. The miniaturized column of claim 4, wherein the first and second detection means comprise apertures having axes orthogonal to the planar surfaces of the substrate, said apertures in combination forming a detection path.

6. The miniaturized column of claim 5, further comprising first and second transparent sheets, wherein the cover plate is interposed between said first transparent sheet and the first planar surface, and said second transparent sheet is disposed over the second planar surface, said transparent sheets in combination with the first and second detection means forming an optical detection path.

7. The miniaturized column of claim 5, comprising further detection means laser-ablated in the first planar surface of the substrate and in communication with the separation compartment and the detection path.

8. The miniaturized column of claim 5, further comprising first and second lightguide means respectively interfaced with the first and second detection means and in communication with the separation compartment.

9. The miniaturized column of claim 7, wherein the further detection means comprises a groove laser-ablated in the first planar surface of the substrate.

10. The miniaturized column of claim 9, further comprising third lightguide means disposed within the further detection means and in communication with the separation compartment and the detection path.

11. The miniaturized column of claim 7, wherein the further detection means comprises a first and second groove laser-ablated in the first planar surface of the substrate, said first and second grooves positioned opposite one another relative to the separation compartment thereby forming a second detection path.

12. The miniaturized column of claim 11, further comprising first and second lightguide means respectively interfaced with the first and second detection means and in communication with the separation compartment, and third and fourth lightguide means respectively disposed within the first and second groove and in communication with the separation compartment and the detection path.

37. The miniaturized column of claim 1, wherein a selected species is chemically bonded to, or adsorbed or deposited on the interior surface of the microchannel.

13. A miniaturized column device comprising:

a substrate having first and second substantially planar opposing surfaces wherein said substrate is comprised of a material other than silicon or silicon dioxide;

first and second microchannels respectively laser-ablated in the first and second planar surfaces;

first and second cover plates disposed respectively over the first and second planar surfaces, said cover plates in combination with the first and second microchannels defining first and second elongate separation compartments;

at least one inlet port communicating with the first separation compartment and at least one outlet port communicating with the second separation compartment; and

conduit means for communicating the first and second separation compartments with each other thereby forming a single continuous separation compartment, said conduit means comprising a laser-ablated aperture in the substrate having an axis which is orthogonal to the planar surfaces.

14. The miniaturized column of claim 13, further comprising first and second detection means comprising apertures laser-ablated respectively in the first and second cover plates and arranged in coaxial communication with the conduit means.

15. The miniaturized column of claim 14, further comprising first and second transparent sheets, wherein the first cover plate is interposed between said first transparent sheet and the first planar surface, and the second cover plate is interposed between said second transparent sheet and the second planar surface.

16. The miniaturized column of claim 15, wherein the conduit means, in combination with the transparent sheets, forms an optical detection path having a pathlength substantially equal to the width of the substrate.

17. The miniaturized column of claim 14, further comprising first and second lightguide means respectively interfaced with the first and second detection means and in communication with the conduit means.

18. The miniaturized column of any one of claims 14, 16 or 17, comprising further detection means formed by a groove laser-ablated in the first planar surface of the substrate and in communication with the conduit means.

19. The miniaturized column of claim 18, further comprising lightguide means disposed within the further detection means and in communication with the conduit means.

38. The miniaturized column of claim 13, wherein a selected species is chemically bonded to, or adsorbed or deposited on the interior surface of the microchannel.

44. The miniaturized column of any one of claims 5, 14 or 26, further comprising first and second communication paths, wherein the first communication path is arranged adjacent to a first side of the separation compartment, and the second communication path is arranged adjacent to a second side of the separation compartment and positioned opposite the first communication path.

45. The miniaturized column of any one of claims 5, 14 or 26, further comprising a first and a second communication path arranged in spaced-apart relation to each other in the longitudinal direction along a first side of the separation channel.

46. The miniaturized column device of any one of claims 5, 14 or 26, further comprising a first coil arranged in coaxial relation about the separation compartment and a second coil arranged in coaxial relation about the separation compartment and in spaced-apart relation to the first coil.

47. The miniaturized column of claim 44, wherein the first and second communication paths are arranged adjacent the detection path.

48. The miniaturized column of claim 14, further comprising a first and a second communication path arranged in spaced-apart relation to each other in the longitudinal direction along a first side of the separation channel, wherein the first and second communication paths are arranged adjacent the conduit means.

49. The miniaturized column of claim 46, wherein the first and second coils are arranged adjacent the first detection means.

20. A miniaturized column device comprising:

a support body formed from a substrate comprised of a material other than silicon or silicon dioxide, said support body having first and second component halves each having substantially planar interior surfaces;

a first microchannel laser-ablated in the interior surface of the first support body half and a second microchannel laser-ablated in the interior surface of the second support body half, wherein each said microchannel is so arranged as to provide the mirror image of the other;

a separation compartment comprising an elongate bore formed by aligning the interior surfaces of the support body halves in facing abutment with each other whereby the microchannels define said elongate bore; and

at least one inlet port and at least one outlet port communicating with the separation compartment, said ports enabling the passage of fluid from an external source through the separation compartment.

21. The miniaturized column of claim 20, further comprising detection means laser-ablated in the support body and in communication with the separation compartment, thereby enabling detection of a sample passing through the separation compartment.

22. The miniaturized column of claim 21, wherein the substrate is selected from the group consisting of polymeric materials, ceramic materials, and combinations thereof.

23. The miniaturized column of claim 22, wherein the support body further comprises fold means for forming a fold in the support body, whereby the substrate may be folded to place the first and second component halves in precise alignment with each other.

24. The miniaturized column of claim 23, wherein the first and second support body halves further comprise micro-alignment means comprising a plurality of holes laser-ablated in the support body halves, wherein the holes are arranged such that coaxial alignment of corresponding holes in the first and second support body halves enables the precise alignment of the support body halves to accurately define the elongate bore.

25. The miniaturized column of claim 23, wherein the first and second support body halves further comprise micro-alignment means comprising corresponding structures formed in the support body halves, said structures comprising a plurality of depressions arranged on the first support body half and a plurality of projections arranged on the second support body half, said projections configured to mate with the depressions such that alignment of the corresponding structures enables the precise alignment of the support body halves to accurately define the elongate bore.

26. The miniaturized column of claim 22, further comprising first and second apertures respectively laser-ablated through the first and second component halves, said apertures communicating with the separation compartment and having axes orthogonal to the plane of the support body, wherein the apertures are arranged to form a coaxial detection path when the interior surfaces of the support body halves are aligned in facing abutment with each other.

27. The miniaturized column of claim 26, further comprising first and second transparent sheets disposed over the exterior of the support body and covering the first and second apertures, whereby a sample passing through the separation compartment can be analyzed by interfacing spectrophotometric detection techniques with the sample through said transparent sheets.

28. The miniaturized column of claim 26, further comprising first and second lightguide means respectively interfaced with the first and second apertures and in communication with the separation compartment.

29. The miniaturized column of any one of claims 26, 27 or 28, comprising further detection means laser-ablated in the interior surface of the support body and in communication with the separation compartment.

30. The miniaturized column of claim 29, wherein the further detection means comprises a groove laser-ablated in the interior surface of the first support body half.

31. The miniaturized column of claim 30, further comprising lightguide means disposed within the further detection means and in communication with the separation compartment.

32. The miniaturized column of claim 29, wherein the further detection means comprises a set of complementary grooves laser-ablated in the interior surface of the first and second support body halves, said grooves communicating with the separation compartment and arranged such that each groove provides the mirror image of the other, whereby said grooves form a further detection path when the interior surfaces of the support body halves are aligned in facing abutment with each other.

33. The miniaturized column of claim 29, wherein the further detection means comprises first and second sets of complementary grooves laser-ablated in the interior surface of the first and second support body halves, said grooves communicating with the separation compartment and arranged such that each respective complementary groove in a set provides the mirror image of the other groove, whereby said groove sets form further detection paths when the interior surfaces of the support body halves are aligned in facing abutment with each other.

34. The miniaturized column of claim 33, wherein the first and second set of complementary grooves are further positioned opposite each other relative to the separation compartment thereby forming a continuous detection path.

35. The miniaturized column of claim 32, further comprising first and second lightguide means respectively interfaced with the first and second apertures and in communication with the separation compartment, and third lightguide means disposed within the further detection means and in communication with the separation compartment.

36. The miniaturized column of claim 34, further comprising first and second lightguide means respectively interfaced with the first and second apertures and in communication with the separation compartment, and third and fourth lightguide means disposed within the further detection means and in communication with the separation compartment.

39. The miniaturized column of claim 20, wherein a selected species is chemically bonded to, or adsorbed or deposited on the interior surface of the microchannel.

40. A miniaturized column device comprising:

a support having first and second substantially planar opposing surfaces, said support having a microchannel laser-ablated in the first planar surface;

a cover plate arranged over the first planar surface, said cover plate in combination with the microchannel defining an elongate separation compartment;

at least one inlet port and at least one outlet port communicating with the separation compartment, said ports enabling the passage of fluid from an external source through the separation compartment; and

a plurality of communication paths arranged adjacent to the separation compartment, said paths enabling detection of changes in the electrical properties of a sample passing through the separation compartment.

41. The miniaturized column device of claim 40, comprising first and second communication paths, wherein the first communication path is arranged adjacent to a first side of the separation compartment, and the second communication path is arranged adjacent to a second side of the separation compartment and positioned opposite the first communication path.

42. The miniaturized column device of claim 40, wherein the plurality of communication paths comprises at least a first and a second communication path arranged in spaced-apart relation to each other in the longitudinal direction along a first side of the separation channel.

43. The miniaturized column device of claim 40, wherein the plurality of communication paths comprises a first coil arranged in coaxial relation about the separation compartment and a second coil arranged in coaxial relation about the separation compartment and in spaced-apart relation to the first coil.

50. A method of forming a miniaturized column device comprising the steps of:

(a) providing a support body having first and second component halves, said support body halves having substantially planar interior surfaces;

(b) forming a compartment in the support body by;

(i) laser ablating a first microchannel in the interior surface of the first support body half;

(ii) laser ablating a second microchannel in the interior surface of the second support body half, wherein the second microchannel is arranged to provide the mirror image of the first microchannel, such that subsequent alignment of the interior surfaces of the support body halves in facing abutment with each other defines an elongate bore;

(c) forming a plurality of ports in the support body, said ports enabling fluid communication between the compartment and associated external fluid containment means, wherein the step comprises laser ablating a plurality of apertures extending from at least one exterior surface of the support body and communicating with at least one microchannel, whereby the apertures permit the passage of fluid therethrough;

(d) forming detection means in the support body by laser ablating further apertures through the first and second component halves, whereby the apertures communicate with the compartment; and

(e) aligning the interior surfaces of the support body halves in facing abutment with each other, thereby aligning the microchannels, ports and detection means to provide a miniaturized column device.

51. The method of claim 50, including the additional step of forming fold means in the support body by laser-ablating a row of spaced-apart perforations in the support body to define a hinge, whereby the support body may be folded about said hinge to place the first and second component halves in precise alignment with each other.

52. The method of claim 51, including the additional step of forming micro-alignment means in the first and second support body halves by laser-ablating holes in the support body halves, wherein said holes are arranged such that coaxial alignment thereof enables the precise alignment of the support body halves to accurately define the elongate bore.

53. The method of claim 51, including the additional step of providing micro-alignment means in the support body halves by forming corresponding structures in the support body halves, wherein the structures comprise a plurality of depressions arranged on the first support body half and a plurality of projections arranged on the second support body half, said projections configured to mate with the depressions such that alignment of the corresponding structures enables the precise alignment of the support body halves to accurately define the elongate bore.

54. The method of claim 50, including the additional step of subjecting the first and second microchannels to a surface treatment after the microchannels are laser ablated in the surface of the support body halves and before the separation compartment is formed, wherein the surface treatment comprises chemical bonding or adsorption of a selected species to the interior surface of the laser-ablated microchannels or thin film deposition of a selected material thereon.

55. The method of claim 50, including the additional steps of:

providing a support body comprising a laminate, said laminate formed from a first layer of polyimide co-extruded with a second, thin layer of a thermal adhesive form of polyimide; and

heat sealing the first and second support body halves together using heat stacking, whereby a weld is formed having substantially the same physical and chemical properties as the support body.