Electronic device for performing active biological operations and method of using same

• US 6,726,880 B1
• Filed: 06/19/2000
• Issued: 04/27/2004
• Est. Priority Date: 11/01/1993
• Status: Expired due to Fees

• Current Assignee: Gamida for Life B.V.
• Original Assignee: Nanogen, Inc.
• Inventors: Ackley, Donald E., Graham, Scott O., Swanson, Paul D., Mather, Elizabeth L., LeClair, Timothy L., Butler, William F.
• Primary Examiner(s): Marschel, Ardin H.
• Application Number:
  US09/596,657
• Time in Patent Office: 1,408 Days
• Field of Search: 422/50, 422/68.1, 422/129, 435/6, 435/7.1
• 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 2219/00617 by chemical means
• 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 2200/025 : Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/0647 : Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0689 : Sealing
• CPC Class Codes: B01L 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 : Electrodes
• CPC Class Codes: B01L 2300/0654 : Lenses; Optical fibres
• 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 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 3/502761 : 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: 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: 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

An electronic device for performing biological operations includes a support substrate and an array of microlocations disposed on the substrate. The array of microlocations include electronically addressable electrodes. A first collection electrode is disposed on the substrate and adjacent to a first side of the array of microlocations. A second collection electrode is disposed on the substrate and adjacent to a second side of the array of microlocations, the second side of the array being opposite of the first side such that the array of microlocations is disposed between the first and second collection electrodes. A flow cell is supported on the substrate. Preferably, the combined area of the collection electrodes is a substantial fraction, preferably at least 50% of the area of the footprint of the flow cell.

Claims

1. An electronic device for performing biological operations comprising:

a support substrate,

an array of microlocations disposed on the substrate, the array of microlocations comprising electronically addressable electrodes,

a first collection electrode disposed on the substrate and adjacent to a first side of the array of microlocations,

a second collection electrode disposed on the substrate and adjacent to a second side of the array of microlocations, the second side of the array being opposite of the first side such that the array of microlocations is disposed between the first collection electrode and the second collection electrode; and

a flow cell, the flow cell adapted to be supported on the substrate.

2. The electronic device for performing active biological operations of claim 1 wherein the collection electrode is a complexity reduction electrode.

3. The electronic device for performing active biological operations of claim 1 further including focusing electrodes.

4. The electronic device for performing active biological operations of claim 1 wherein the flow cell defines a footprint such that the combined area of the first collection electrode and second collection electrodes in proportion to the footprint of the flow cell is at least 50%.

5. The electronic device for performing active biological operations of claim 1 wherein the flow cell defines a footprint such that the combined area of the first collection electrode and second collection electrodes in proportion to the footprint of the flow cell is at least 60%.

6. The electronic device for performing active biological operations of claim 1 wherein the flow cell includes an inlet.

7. The electronic device for performing active biological operations of claim 1 wherein the flow cell includes an outlet.

8. A method for analysis of a biological sample utilizing an electronic device for performing active biological operations, the device including a support substrate, an array of microlocations disposed on the substrate, the array of microlocations comprising electronically addressable electrodes a first collection electrode disposed on the substrate and adjacent to a first side of the array microlocations, and a second collection electrode disposed on the substrate and adjacent a second side of the array of microlocations, the second side of the array being opposite of the first side such that the array of microlocations is disposed between the first collection electrode and the second collection electrode, the method comprising the steps of:

providing the sample to the device,

placing the first collection electrode attractive relative to charged biological materials, thereby concentrating charged biological materials on the first collection electrode,

placing the second collection electrode attractive to charged biological materials, thereby transporting said charged biological materials from the first collection electrode towards the second collection electrode, and over at least a portion of said array of microlocations disposed on the substrate, whereby interaction between the charged biological materials and the array occurs.

9. The method for analysis of a biological sample of claim 8 utilizing an electronic device for performing active biological operations, wherein the electrodes of the array are maintained electrically passive.

10. The method for analysis of a biological sample of claim 8 utilizing an electronic device for performing active biological operations, wherein the electrodes of the array are electrically active to facilitate interaction between the array and the charged biological material.

11. The method for analysis of a biological sample of claim 8 utilizing an electronic device for performing active biological operations, wherein the charged biological material is moved over the array as a wave.

12. The method for analysis of a biological sample of claim 8 utilizing an electronic device for performing active biological operations, wherein the charged biological material is moved over the array and held in place over the array.

13. The method for analysis of a biological sample according to claim 8 further comprising the step of applying an alternating current field between the first and second collection electrodes so as to hold the charged biological materials over the array.

14. The method for analysis of a biological sample according to claim 8, wherein when the second collection electrode is placed attractive relative to charged biological material, the first collection electrode is placed repulsive relative to charged biological material, thereby concentrating charged biological species on the second collection electrode.

15. The method for analysis of a biological sample according to claim 8 further comprising the additional steps of placing the second collection electrode repulsive relative to charged biological material and placing the first collection electrode attractive relative to charged biological material, thereby concentrating charged biological species on the first collection electrode.