System including functionally separated regions in electrophoretic system

• US 6,319,472 B1
• Filed: 12/02/1998
• Issued: 11/20/2001
• Est. Priority Date: 11/01/1993
• Status: Expired due to Fees

• Current Assignee: Nanogen, Inc.
• Original Assignee: Nanogen, Inc.
• Inventors: Ackley, Donald E., Sheldon, Edward L., Krihak, Michael K.
• Primary Examiner(s): Marschel, Ardin H.
• Application Number:
  US09/203,935
• Time in Patent Office: 1,084 Days
• Field of Search: 422/50, 422/68.1, 435/283.1, 435/285.1, 435/285.2, 435/286.1, 435/286.2, 435/286.5, 435/287.1, 435/287.2, 435/289.1, 435/299.1, 435/303.1
• US Class Current: 422/68.1
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00614 Delimitation of the attachment areas
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00686 Automatic
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00702 : Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00713 : Electrochemical synthesis
• CPC Class Codes: B01J 2219/0072 : Organic compounds
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00731 : Saccharides
• CPC Class Codes: B01L 2200/0647 : Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0684 : Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 : Electrodes
• CPC Class Codes: B01L 2300/0816 : Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0877 : Flow chambers
• CPC Class Codes: B01L 2300/0887 : Laminated structure
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0421 : electrophoretic flow
• CPC Class Codes: B01L 2400/0424 : Dielectrophoretic forces
• CPC Class Codes: B01L 2400/0475 : specific mechanical means and fluid pressure
• 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 3/502723 : characterised by venting arrangements
• 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 3/502738 : characterised by integrated valves microvalves F16K99/0001
• 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: B01L 3/502761 : specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: B82Y 10/00 : Nanotechnology for information processing, storage or transmission, e.g. quantum computing or single electron logic
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07B 2200/11 : Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07K 1/04 : on carriers C07K1/003, C07K1/006 take precedence
• CPC Class Codes: C07K 1/045 : using devices to improve synthesis, e.g. reactors, special vessels
• CPC Class Codes: C07K 1/047 : Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C12Q 1/6813 : Hybridisation assays
• CPC Class Codes: C12Q 1/6816 : characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6825 : Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2565/515 : characterised by the interaction between or sequential use of two or more arrays
• CPC Class Codes: C12Q 2565/607 : being a sensor, e.g. electrode
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: F04B 19/006 : Micropumps F04B43/043 and F04B43/095 take precedence
• CPC Class Codes: G01N 27/44743 : Introducing samples
• CPC Class Codes: G11C 13/0014 : comprising cells based on organic memory material
• CPC Class Codes: G11C 13/0019 : comprising bio-molecules
• CPC Class Codes: G11C 13/04 : using optical elements ; using other beam accessed elements, e.g. electron or ion beam
• CPC Class Codes: G11C 19/00 : Digital stores in which the information is moved stepwise, e.g. shift registers
• CPC Class Codes: H01L 25/50 : Multistep manufacturing processes of assemblies consisting of devices, each device being of a type provided for in group H01L27/00 or H01L29/00 H01L21/50 takes precedence
• CPC Class Codes: H01L 2924/00 : Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
• CPC Class Codes: H01L 2924/0002 : Not covered by any one of groups H01L24/00, H01L24/00 and H01L2224/00

Abstract

Methods, apparatus, and applications for use of a stacked, reconfigurable system for electrophoretic transport are provided. In one embodiment, a system having a first chamber including at least a bottom support and an intermediate support, and a second chamber, said second chamber including a bottom support and a top member, the first and second chambers being coupled through a via. Electrophoretic, and optional electro-osmotic and thermal, transport is effected. In another aspect of this invention, three or more chambers are coupled by an electrophoretic buss. The electrophoretic buss includes driving electrodes and is adapted to receive fluid containing materials for transport. The chambers are coupled to the electrophoretic buss and serve as a tap from the buss for delivery of charged materials. In one embodiment, certain functions are performed in different chambers. For example, the first chamber may receive the sample and perform sample processing functions, the second chamber may perform amplification procedures, yet a third chamber may perform hybridization or other assays, and yet another chamber may perform immunoassays. By separating various functions to different chambers, speed and sensitivity may be improved. In yet another aspect of this invention, analysis from a earlier stage may be utilized in a subsequent stage to reconfigure the system for optimum use. In one application, analysis at a first level is utilized to determine an action at a second level, such as the synthesis of a compound. The synthesized compound in response to a biohazard may comprise vaccine or antidote.

Claims

1. A stacked, multilayer, electronically reconfigurable system for electrophoretic transport of charged biological material comprising:

a first chamber adapted for preparation of said biological material, said first chamber including at least one individually controllable electrode;

a second chamber stacked on top of said first chamber and adapted for sorting of said biological material, obtained at least in part from said first chamber, said second chamber including at least one individually controllable electrode, and wherein said second chamber further includes a dielectrophoresis system for sorting of said biological material;

a third chamber stacked on top of said second chamber adapted for analysis of said biological material obtained at least in part from said second chamber, said third chamber including at least one individually controllable electrode;

an inlet coupled to said first chamber and further coupled to a source of the biological material; and

wherein the first, second and third chambers being in fluidic coupling with each other through a plurality of vias.

2. A stacked, multilayer, electronically, reconfigurable system of claim 1 wherein said first chamber includes a filter for removal of extraneous material.

3. A stacked, multilayer, electronically reconfigurable system of claim 1 wherein said first chamber includes an affinity membrane.

4. A stacked, multilayer, electronically reconfigurable system of claim 1 wherein said dielectrophoresis system further serves to lyse biological material.

5. A stacked, multilayer, electronically reconfigurable system of claim 4 wherein said biological material includes cells.

6. A stacked, multilayer, electronically reconfigurable system of claim 1 wherein said third chamber includes a diagnostic assay.

7. A stacked, multilayer, electronically reconfigurable system of claim 6 wherein said diagnostic assay includes a DNA hybridization assay.

8. A stacked, multilayer, electronically reconfigurable system of claim 6 wherein said diagnostic assay includes an immunoassay.

9. A stacked, multilayer, electronically reconfigurable system of claim 1 further including a chamber adapted for amplification of said biological material.

10. A stacked, multilayer, electronically reconfigurable system of claim 1 wherein the fluidic coupling comprises a via connecting the first chamber and the second chamber and another via connecting the second chamber and the third chamber.

11. A stacked, multilayer, electronically reconfigurable system of claim 1 further including an electrophoretic buss, said buss including a chamber region spanning the first, second, and third chambers, said first, second, and third chambers being in fluidic contact with said electrophoretic buss.

12. A stacked, multilayer, electronically reconfigurable device for electrophoretic transport of charged biological material comprising:

a plurality of stacked, adjacent chambers, wherein the stacked, adjacent chambers are stacked on top of one another, said chambers being separated from one another by intermediate members formed of a nonporous material, each chamber defining a bounded volume for providing a controlled flow of charged biological material;

an inlet port coupling to one of the plurality of chambers;

an outlet port coupling to one the plurality of chambers;

a plurality of vias connecting one or more of said chambers, said vias being located in the intermediate members and providing fluidic communication between adjacent chambers; and

at least one individually controllable electrode located in each of the plurality of chambers, the electrodes producing localized electromagnetic environments to transport said charged biological material.

13. A stacked, multilayer, electronically reconfigurable device according to claim 12 further comprising an electrophoretic buss spanning at least two of the plurality of chambers, said electrophoretic buss including a chamber providing a volume for the electrophoretic transport of said charged biological material into one or more of the plurality of chambers.

14. A stacked, multilayer, electronically reconfigurable device according to claim 13, the electrophoretic buss further including a plurality of driving electrodes disposed on substantially opposite ends of the electrophoretic buss, the driving electrodes producing a localized electromagnetic environment to affect the flow of charged biological material through the electrophoretic buss.

15. A stacked, multilayer, electronically reconfigurable device according to claim 14 further including a plurality of collection electrodes located in the plurality of chambers, said plurality of collection electrodes also being located adjacent to the periphery of the electrophoretic buss, said plurality of collection electrodes serving as taps for the charged biological material from the electrophoretic buss to one or more of said chambers.

16. A stacked, multilayer, electronically reconfigurable device according to claim 12, wherein at least one of the individually controllable electrodes includes an electrode through region therein.

17. A stacked, multilayer, electronically reconfigurable device according to claim 16, wherein at least one of the individually controllable electrodes includes an electrode through region being positioned directly adjacent to, and in fluidic communication with the inlet port.

18. A stacked, multilayer, electronically reconfigurable device according to claim 16, wherein at least one of the individually controllable electrodes includes an electrode through region being in fluidic communication with the outlet port and wherein said at least one of the individually controllable electrodes circumscribes the electrode through region.

19. A stacked, multilayer, electronically reconfigurable device according to claim 12 further including a permeation layer covering the electrodes.

20. A stacked, multilayer, electronically reconfigurable device according to claim 12 further including one or more affinity materials disposed throughout the device.

21. A stacked, multilayer, electronically reconfigurable device according to claim 20 further including an affinity matrix coated onto or near one or more of said plurality of electrodes.

22. A stacked, multilayer, electronically reconfigurable device according to claim 20 further including an affinity matrix coated onto or near one or more of said plurality of vias.

23. A stacked, multilayer, electronically reconfigurable device according to claim 13 further including an affinity matrix located in said electrophoretic buss.

24. A stacked, multilayer, electronically reconfigurable device according to claim 12 further including at least one separation membrane located in at least one via for separating small charged species from macromolecules included in the biological material.

25. A stacked, multilayer, electronically reconfigurable device according to claim 13 further including at least one separation membrane located in said electrophoretic buss for separating small charged species from macromolecules included in the biological material.

26. A stacked, multilayer, electronically reconfigurable device according to claim 19 further including a hybridization target in the permeation layer, said hybridization target selected from the group consisting of DNA probes, RNA probes, antigens, antibodies, enzymes, and peptides.

27. A stacked, multilayer, electronically reconfigurable device according to claim 12, wherein the chamber coupled to the inlet port is used for sample preparation.

28. A stacked, multilayer, electronically reconfigurable device according to claim 27, wherein sample preparation includes a processing step selected from the group consisting of filtering, diluting, screening, and sorting.

29. A stacked, multilayer, electronically reconfigurable device according to claim 12, wherein at least one chamber is used to amplify one or more components of said biological material.

30. A stacked, multilayer, electronically reconfigurable device according to claim 12, wherein at least one chamber is used for one or more assays of said biological material.

31. A stacked, multilayer, electronically reconfigurable device according to claim 12 further including one or more assay chips located in at least one of said plurality of chambers.

32. A stacked, multilayer, electronically reconfigurable device according to claim 12 further including one or more immunoassay sites in at least one of said plurality of chambers.

33. A multilayer, electronically reconfigurable device for electrophoretic transport of charged biological material comprising:

a plurality of stacked, adjacent chambers, wherein the stacked, adjacent chambers are stacked on top of one another, each chamber defining a bounded volume for providing a controlled flow of charged biological material;

an inlet port coupling to one of the plurality of chambers;

an outlet port coupling to one the plurality of chambers;

a plurality of vias connecting one or more of said chambers, said vias providing fluidic communication between adjacent chambers;

a plurality of electrodes located in at least one of the plurality of chambers, the plurality of electrodes producing localized electromagnetic environments to generate a reconfigurable flow pattern; and

at least one assay located in the plurality of chambers.

34. A stacked, multilayer, electronically reconfigurable system for electrophoretic transport of charged biological materials comprising:

a first chamber defined by a bottom support, an intermediate member and a first spacer;

an inlet coupling said first chamber to a source of biological materials;

a second chamber stacked on top of said first chamber, said second chamber defined by the intermediate member of said first chamber, a top member, and a second spacer;

an outlet coupled to said second chamber;

at least one via formed in the intermediate member, wherein said first chamber and said second chamber are fluidically coupled through the at least one via; and

a first individually controllable electrode disposed in either said first chamber or said second chamber, said first individually controllable electrode disposed directly opposite said at least one via.

35. The system of claim 34, further comprising a second individually controllable electrode disposed on the intermediate member adjacent to said at least one via.

36. The system of claim 34, wherein said inlet is coupled to said first chamber via an aperture located on the bottom support.

37. The system of claim 34, wherein said outlet is coupled to said second chamber via an aperture disposed in the top member.

38. The system of claim 36, further comprising a second individually controllable electrode disposed in the first chamber on the intermediate member, said second individually controllable electrode located directly opposite the aperture.

39. The system of claim 37, further comprising a second individually controllable electrode disposed in the second chamber on the intermediate member, said second individually controllable electrode located directly opposite the aperture.