Integrated electrokinetic devices and methods of manufacture

• US 7,214,300 B2
• Filed: 06/04/2001
• Issued: 05/08/2007
• Est. Priority Date: 06/04/2001
• Status: Active Grant

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Epocal Incorporated (Siemens AG)
• Inventors: Lauks, Imants R
• Primary Examiner(s): CHOI, LING SIU
• Application Number:
  US09/871,821
• Publication Number:
  US 20020179448A1
• Time in Patent Office: 2,164 Days
• Field of Search: 204/400, 204/600, 204/519, 204/543, 204/544
• US Class Current: 204/519
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00853 Employing electrode arrangements
• CPC Class Codes: B01J 2219/0086 Dimensions of the flow channels
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2300/10 Means to control humidity and/or other gases
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• 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 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"

Abstract

Devices with electrokinetic elements are disclosed as well as their method of microfabrication for use in micro-scale analysis, mixture separation and reaction. The devices consist of solid hydrophilic-matrix films that have been microfabricated into a variety of micro-scale structures. These structures include hydrophilic-matrix conductors for electrokinetic species transport and separation. They also include hydrophilic-matrix cladding containing chemical species adjacent to either an open conduit or a hydrophilic matrix conductor. Also described are other integrated microstructures consisting of hydrophilic-matrix materials such as micro-reaction zones for retaining chemical species for on-chip chemical reactions and integrated detection structures for on-chip species detection. In general, a hydrophilic matrix on a substrate functions as a conductor that is covered by an electrically insulating, preferably water permeable material.

Claims

1. An integrated electrokinetic circuit for transport of an aqueous solute, comprising a device for electrokinetic transport of an aqueous solute, the device comprising

an electrically insulating substrate;

a conductor element for electrokinetic transport of the solute, the conductor element being in the form of a solid hydrophilic-matrix layer on the substrate, the matrix layer being in a substantially dry, inactive state wherein electrokinetic transport is substantially prevented and having a first surface engaging the substrate and a second surface; and

a cover layer for electrically insulating and covering the second surface, the cover layer being impermeable to the solute;

whereby exposure of the hydrophilic matrix to water converts the matrix from the inactive state to a hydrated, active state permitting electrokinetic transport of the solute.

2. The integrated circuit as defined in claim 1, further comprising a means for introducing water into the conductor element.

3. The integrated circuit of claim 1, wherein the hydrophilic solid matrix layer is micro-fabricated onto the substrate.

4. The integrated circuit of claim 1, wherein the hydrophilic-solid matrix layer is a dry reagent film.

5. The integrated circuit of claim 1, wherein the cover layer is micro-fabricated onto the conductor element and the substrate.

6. The integrated circuit of claim 1, wherein at least one of the cover layer and the substrate has at least one portion which is permeable to water vapor.

7. The integrated circuit of claim 1, further including a pair of spaced apart electrodes in electric contact with the conductor element at spaced apart locations for applying an electric potential across the conductor element.

8. The integrated circuit of claim 6, wherein the electrodes are applied to the substrate, and the device further includes an insulator layer for electrically insulating each electrode, the insulator layer having an opening in each region of overlap between one of the electrodes and the conductor element for permitting electric contact of the conductor element with the integral electrodes for electrokinetic pumping.

9. The integrated circuit of claim 1, wherein the substrate is made of electrically insulating material.

10. The integrated circuit of claim 1, wherein the substrate includes a layer of electrically conductive material and a layer of electrically insulating material intermediate the layer of conductive material and the conductor element.

11. The integrated circuit of claim 1, further comprising an input region for supply of solute into the conductor element and an output region spaced apart therefrom for removal of transported solute from the conductor element.

12. The integrated circuit of claim 11, wherein the hydrophilic matrix of the conductor element is water-insoluble in the input and output regions.

13. The integrated circuit of claim 12, wherein the conductor element further comprises a reservoir region intermediate the input and output regions and including at least one chemical reactant for interaction with the transported solute.

14. The integrated circuit of claim 13, further comprising an electrode for applying an electric potential to the reservoir region.

15. The integrated circuit of claim 14, comprising first and second conductor elements, the first conductor element including the reservoir region and the second conductor element overlapping the first conductor element in a reaction region for uptake of a preselected reaction product created in the reaction region between the reactant and the solute.

16. The integrated circuit of claim 1, further comprising a first reservoir region adjacent one of the input and output regions and including a chemical reactant for interaction with the transported solute.

17. The integrated circuit of claim 16, further comprising a pair of electrodes for the conductor element for selectively applying a potential to the conductor element for driving electrokinetic solute transport from the input region to the output region.

18. The integrated circuit of claim 17, wherein the conductor element further comprises a second reservoir region located intermediate the input and output region of the conductor element and including at least one chemical reactant for interaction with the transported solute.

19. The integrated circuit of claim 18, further comprising an electrode for applying an electric potential to at least one of the first and second reservoir regions.

20. The integrated circuit of claim 13, wherein the reservoir region includes chemical reactants for performing a nucleic acid amplification or sequencing reaction.

21. The integrated circuit of claim 16 or 18, wherein at least the first reservoir region includes chemical reactants for performing a nucleic acid amplification or sequencing reaction.

22. The integrated circuit of claim 16, including a plurality of conductor elements, each conductor element having an associated reservoir region for contact with a sample solution including the chemical reactant.

23. The integrated circuit of claim 1, further comprising a pair of spaced apart electrokinetic electrodes for applying an electric potential to the conductor element for displacing along the conductor element the solvent containing the solute species.

24. The integrated circuit of claim 22, wherein the plurality of conductor elements and processing regions are constructed as a ligand-binding array and the sample solution contains species for binding with ligands associated with the ligand binding array.

25. The integrated circuit of claim 24, wherein the ligand-binding array is selected from the group of antibody arrays, DNA arrays and RNA arrays.

26. The integrated circuit of claim 23, including a plurality of conductor elements, each conductor element having a pair of associated electrokinetic electrodes, and each pair of electrodes being separately controlled for individual control of the solvent transport in the respectively associated conductor element.

27. An integrated electrokinetic circuit for transport of an aqueous solute, comprising a plurality of devices for electrokinetic transport of an aqueous solute, each device comprising

an electrically insulating substrate;

a conductor element for electrokinetic transport of the solute, the conductor element being in the form of a solid hydrophilic-matrix layer on the substrate, the matrix layer being in a substantially dry, inactive state wherein electrokinetic transport is substantially prevented and having a first surface engaging the substrate and a second surface; and

a cover layer for electrically insulating and covering the second surface, the cover layer being impermeable to the solute;

whereby exposure of the hydrophilic matrix to water converts the matrix from the inactive state to a hydrated, active state permitting electrokinetic transport of the solute.

28. The integrated circuit as defined in claim 27, wherein the conductor elements do not overlap.

29. The integrated circuit as defined in claim 27, wherein at least a pair of conductor elements intersect and are in contact with each other for exchange of transported solute species.

30. The integrated circuit as defined in claim 27, wherein at least a pair of the conductor elements intersect and are insulated from each other for preventing electrical contact and solute species exchange.

31. The integrated circuit of claim 30, further comprising a means for introducing the aqueous solute into the conductor element.