Fully integrated miniaturized planar liquid sample handling and analysis device

• US 5,571,410 A
• Filed: 06/07/1995
• Issued: 11/05/1996
• Est. Priority Date: 10/19/1994
• Status: Expired

• 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): Therkorn, Ernest G.
• Application Number:
  US08/486,024
• Time in Patent Office: 517 Days
• Field of Search: 204/601, 204/602, 204/603, 204/604, 204/605, 204/451, 204/452, 204/453, 204/454, 204/455, 204/456, 210/635, 210/656, 210/659, 210/198.2, 422/68.1, 422/69, 422/70
• US Class Current: 210/198.2
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• 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 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0442 thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• 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: 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 27/44708 : 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

Abstract

A miniaturized total analysis system ("μ-TAS") comprising a miniaturized planar column device is described for use in liquid phase analysis. The μ-TAS comprises microstructures fabricated by laser ablation in a variety of novel support substrates. The μ-TAS includes associated laser-ablated features required for integrated sample analysis, such as analyte detection means and fluid communication means. μ-TAS constructed according to the invention is useful in any analysis system for detecting and analyzing small and/or macromolecular solutes in the liquid phase and may employ chromatographic separation means, electrophoretic separation means, electrochromatographic separation means, or combinations thereof.

Claims

1. A miniaturized total analysis system (μ

-TAS) comprising a miniaturized column device comprising;

(a) 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 first microchannel laser-ablated in the first planar surface, wherein said first microchannel comprises more than one sample handling region;

(b) a cover plate arranged over the first planar surface, said cover plate in combination with the first microchannel forming a first sample processing compartment, wherein the sample handling regions define a sample flow component in fluid communication with a sample treatment component; and

(c) at least one inlet port and at least one outlet port communicating with the first sample processing compartment, said inlet and outlet ports enabling the passage of fluid from an external source through the sample processing compartment.

2. The μ

-TAS of claim 1, wherein said first sample processing compartment comprises a serial arrangement of sample handling regions which define a serial arrangement of alternating sample flow components and sample treatment components.

3. The μ

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

4. The μ

-TAS of claim 3, further comprising detection means laser ablated in the substrate, wherein said detection means is in communication with the sample flow component thereby enabling the detection of a sample passing through the sample processing compartment.

5. The μ

-TAS of claim 3, further comprising access ports in fluid communication of the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component.

6. The μ

-TAS of claim 2, further comprising access ports in fluid communication with the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component.

7. The μ

-TAS of claim 2, further comprising;

(a) a reservoir microstructure laser-ablated in the first planar surface, wherein the cover plate in combination with said microstructure define a reservoir compartment having an inlet means and an outlet means;

(b) a conducting microchannel laser-ablated in the first planar surface, wherein the cover plate in combination with said conducting microchannel defines a sample flow component having first and second ends respectively in fluid communication with the sample processing compartment and the reservoir compartment outlet means;

(c) an orifice in divertable fluid communication with the reservoir compartment inlet means, said orifice enabling the passage of fluid from an external source into the reservoir compartment; and

(d) a motive means enabling the displacement of a fluid from the reservoir compartment through the sample flow component and into the first sample processing compartment.

8. The μ

-TAS of claim 7, further comprising;

(a) a sample delivery means in fluid communication with the first sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;

(b) a fluid source in divertable fluid communication with the fluid communication means; and

(c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means.

9. The μ

-TAS of claim 2, further comprising;

(a) a sample delivery means in fluid communication with the first sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;

(b) a fluid source in divertable fluid communication with the fluid communication means; and

(c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means.

10. The μ

-TAS of claim 2, further comprising;

(a) a second microchannel having an inlet port and an outlet port laser ablated in the second planar surface;

(b) a second cover plate disposed over the second planar surface, said cover plate in combination with the second microchannel defining a second sample processing compartment;

(c) conduit means for communicating the outlet port of the first sample processing compartment and the inlet port of the second sample processing compartment with each other thereby forming a single continuous sample processing compartment, said conduit means comprising a laser-ablated aperture in the substrate, said aperture having an axis which is orthogonal to the planar surfaces.

11. The μ

-TAS of claim 10, further comprising detection means comprising apertures laser-ablated respectively in the first and second cover plates and arranged in co-axial communication with the conduit means.

12. The μ

-TAS of claim 11, further comprising access ports in fluid communication of the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component.

13. The μ

-TAS of claim 10, further comprising access ports in fluid communication with the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component.

14. The μ

-TAS of claim 10, further comprising;

(a) a reservoir microstructure laser-ablated in the first planar surface, wherein the cover plate in combination with said microstructure define a reservoir compartment having an inlet means and an outlet means;

(b) a conducting microchannel laser-ablated in the first planar surface, wherein the cover plate in combination with said conducting microchannel defines a sample flow component having first and second ends respectively in fluid communication with the sample processing compartment and the reservoir compartment outlet means;

(c) an orifice in divertable fluid communication with the reservoir compartment inlet means, said orifice enabling the passage of fluid from an external source into the reservoir compartment; and

(d) a motive means enabling the displacement of a fluid from the reservoir compartment through the sample flow component and into the first sample processing compartment.

15. The μ

-TAS of claim 14, further comprising;

(a) a sample delivery means in fluid communication with the first sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;

(b) a fluid source in divertable fluid communication with the fluid communication means; and

(c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means.

16. The μ

-TAS of claim 10, further comprising;

(a) a sample delivery means in fluid communication with the first sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;

(b) a fluid source in divertable fluid communication with the fluid communication means; and

(c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means.

17. A μ

-TAS device comprising;

(a) 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;

(b) 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 said first and second microchannels are arranged so as to provide the mirror image of the other;

(c) a sample processing compartment formed by aligning the interior surfaces of the support body halves in facing abutment with each other whereby the microchannels define said sample processing compartment and wherein said sample processing compartment comprises sample handling regions which define a sample flow component in fluid communication with a sample treatment component; and

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

18. The μ

-TAS of claim 17, wherein said sample processing compartment comprises a serial arrangement of sample handling regions which define a serial arrangement of alternating sample flow components and sample treatment components.

19. The μ

-TAS of claim 18, further comprising detection means laser ablated in the substrate, wherein said detection means is in communication with the sample processing compartment thereby enabling the detection of a sample passing through the sample processing compartment.

20. The μ

-TAS of claim 19, further comprising detection means laser ablated in the substrate, wherein said detection means is in communication with the sample flow component thereby enabling the detection of a sample passing through the sample processing compartment.

21. The μ

-TAS of claim 19, further comprising access ports in fluid communication of the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component.

22. The μ

-TAS of claim 18, further comprising access ports in fluid communication with the sample flow component, thereby enabling the passage of fluid between an external source and the sample flow component.

23. The μ

-TAS of claim 18, further comprising;

(a) a reservoir microstructure laser-ablated in the first planar surface, wherein the cover plate in combination with said microstructure define a reservoir compartment having an inlet means and an outlet means;

(b) a conducting microchannel laser-ablated in the first planar surface, wherein the cover plate in combination with said conducting microchannel defines a sample flow component having first and second ends respectively in fluid communication with the sample processing compartment and the reservoir compartment outlet means;

(c) an orifice in divertable fluid communication with the reservoir compartment inlet means, said orifice enabling the passage of fluid from an external source into the reservoir compartment; and

(d) a motive means enabling the displacement of a fluid from the reservoir compartment through the sample flow component and into the sample processing compartment.

24. The μ

-TAS of claim 23, further comprising;

(a) a sample delivery means in fluid communication with the sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;

(b) a fluid source in divertable fluid communication with the fluid communication means; and

(c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means.

25. The μ

-TAS of claim 18, further comprising;

(a) a sample delivery means in fluid communication with the sample processing compartment outlet port, said sample delivery means comprising a mixing chamber in fluid communication and in axial alignment with a fluid communication means and an outlet nozzle;

(b) a fluid source in divertable fluid communication with the fluid communication means; and

(c) a post-column collection device comprising a sample receiving means positioned relative to the outlet nozzle to receive eluent from the nozzle means.