Control system for active programmable electronic microbiology system

• US 6,582,660 B1
• Filed: 05/20/1997
• Issued: 06/24/2003
• Est. Priority Date: 11/01/1993
• Status: Expired due to Fees

• Current Assignee: Gamida for Life B.V.
• Original Assignee: Nanogen, Inc.
• Inventors: Tu, Eugene, Heller, Michael J.
• Primary Examiner(s): Marschel, Ardin H.
• Application Number:
  US08/859,644
• Time in Patent Office: 2,226 Days
• Field of Search: 422/50, 422/68.1, 435/6, 435/91.2, 435/7.1, 435/810, 436/501, 935/77, 935/78, 935/88, 935/85
• 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 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00614 Delimitation of the attachment areas
• 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 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• CPC Class Codes: B01J 2219/00644 the porous medium being present in discrete locations, e.g. gel pads
• 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 2219/00713 : 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: B01J 2219/00783 : Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00828 : Silicon wafers or plates
• CPC Class Codes: B01J 2219/00853 : Employing electrode arrangements
• CPC Class Codes: B01L 2200/025 : Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/143 : Quality control, feedback systems
• 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 2300/0838 : Capillaries
• CPC Class Codes: B01L 2300/0877 : Flow chambers
• CPC Class Codes: B01L 2400/0421 : electrophoretic flow
• 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 3/502761 : 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: 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
• CPC Class Codes: H01L 2924/09701 : Low temperature co-fired ceramic [LTCC]

Abstract

A system for performing molecular biological diagnosis, analysis and multi-step and multiplex reactions utilizes a self-addressable, self-assembling microelectronic system for actively carrying out controlled reactions in microscopic formats. These reactions include most molecular biological procedures, such as nucleic acid hybridization, antibody/antigen reaction, and clinical diagnostics. Multi-step combinatorial biopolymer synthesis may be performed. A controller interfaces with a user via input/output devices, preferably including a graphical display. Independent electronic control is achieved for the individual microlocations. In the preferred embodiment, the controller interfaces with a power supply and interface, the interface providing selective connection to the microlocations, polarity reversal, and optionally selective potential or current levels to individual electrodes. A system for performing sample preparation, hybridization and detection and data analysis integrates multiple steps within a combined system.

Claims

1. A controlled addressable, programmable electronic matrix device system having a plurality of individually addressable electrodes, comprising:

a power supply,

a user input system for receiving user input and generating an output corresponding thereto,

a controller adapted to receive the output from the input system and provide output including control signals utilized to generate independent electronic environments at the electrodes of the matrix device, the control signals including information relating to at least one parameter selected from the group consisting of;

polarity, the presence or absence of a connection between the power supply and an individual electrode, and the amount of current or potential supplied to the individual electrode,

an interface adapted to connect the output of the controller to the matrix device, and

an active, programmable electronic matrix device, the matrix device comprising;

a plurality of contact pads for contacting the interface and receiving the control signals,

a substrate, the substrate supporting the plurality of individually addressable electrodes, wherein the plurality of individual addressable electrodes have a permeation layer disposed thereon,

biological capture probes disposed attached to the permeation layer for interacting with the specific binding entities;

and an illumination source operatively positioned to provide radiation to the active matrix device.

2. The control system of claim 1 wherein a circuit element is located proximate to said addressable electrode.

3. The control system of claim 1 wherein the power supply is a regulated power supply.

4. The control system of claim 1 wherein the power supply is a sourced current generator.

5. The control system of claim 1 wherein the power supply comprises a waveform generator.

6. The control system of claim 1 wherein the circuit element includes a relay.

7. The control system of claim 1 wherein the circuit elements include a relay to provide selective connection from the power supply to the electrodes.

8. The control system of claim 1 wherein the circuit elements include a relay adapted to change the polarity of the output of the power supply.

9. The control system of claim 1 wherein the circuit elements include a relay to provide selective connection to either a first level or second level of a signal.

10. The control system of claim 9 wherein the signal is a predetermined voltage level.

11. The control system of claim 9 wherein the signal comprises current at a predetermined level.

12. The control system of claim 1 wherein the control signals include digital signals.

13. The control system of claim 1 wherein the control signals include analog signals.

14. The control system of claim 4 wherein the sourced current generator provides multiple sources of current.

15. The control system of claim 14 wherein the multiple sources of current include different levels of current.

16. The control system of claim 14 wherein the multiple sources of current include current waveforms.

17. The control system of claim 1 wherein the controller comprises a computer.

18. The control system of claim 1 wherein the controller is microprocessor based.

19. The control system of claim 1 further including an output system for providing information to the user.

20. The control system of claim 1 wherein the output system includes a display.

21. The control system of claim 1 further including a detection system, said illumination source being under control of said controller.

22. The control system of claim 1 wherein the said user instructions include an indication of polarity information for at least one said addressable electrode.

23. The control system of claim 1 wherein said controller comprises circuit elements integrated into an underlying semiconductor support.