Devices for molecular biological analysis and diagnostics including waveguides

• US 6,315,953 B1
• Filed: 01/29/1999
• Issued: 11/13/2001
• 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., Butler, William F., Swanson, Paul D.
• Primary Examiner(s): Marschel, Ardin H.
• Application Number:
  US09/240,931
• Time in Patent Office: 1,019 Days
• Field of Search: 422/052, 422/68.1, 435/183.1, 435/6, 435/287.1, 435/287.2, 435/287.3, 435/287.7, 435/287.8, 435/287.9, 435/289.1
• 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 2200/0689 : 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 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0645 : Electrodes
• CPC Class Codes: B01L 2300/0654 : Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0877 : Flow chambers
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• 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: 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

An electronic device for performing active biological operations includes a support substrate, a second substrate, a source of illumination, and an edge illumination layer. The support substrate includes first and second surfaces and a via between the first and second surfaces to permit fluid flow through the substrate. The second substrate includes a first surface that is adapted to be disposed in facing arrangement with the second surface of the first substrate. The second substrate includes an array of microlocations wherein the array is adapted to receive the fluid. A sealant is disposed between the second face of the support substrate and the first face of the second substrate. The device includes a source of illumination and an edge illumination layer having an input adapted to receive the illumination from the source, and an output adapted to direct the illumination to the array. The edge illumination layer is disposed adjacent to and between the support substrate and the second substrate. The illumination from the edge illumination layer is directed substantially parallel to the support substrate and second substrate and illuminates the array.

Claims

1. An electronic device for performing active biological operations, comprising:

a support substrate having a first and second surface, and a via between the first and second surfaces to permit fluid flow through the substrate,

a second substrate including at least a first surface, the first surface being adapted to be disposed in facing arrangement with the second surface of the first substrate, the second substrate including an array of microlocations disposed on the first surface of the second substrate, the array being adapted to receive said fluid,

a sealant disposed between the second face of the support substrate and the first face of the second substrate,

a source of illumination, and

an edge illumination layer having an input adapted to receive the illumination from the source, and a terminal edge which is disposed toward the first surface of the second substrate, the edge illumination layer being adjacent to the support substrate and disposed between the support substrate and the second substrate, the illumination from the edge illumination layer being directed substantially parallel to the support substrate and the second substrate so as to illuminate the array.

2. The electronic device for performing active biological operations of claim 1 wherein the source of illumination is a laser.

3. The electronic device for performing active biological operations of claim 2 wherein the laser is a laser bar.

4. The electronic device for performing active biological operations of claim 1 wherein the edge illumination layer is affixed to the support substrate.

5. The electronic device for performing active biological operations of claim 4 wherein the edge illumination layer is a polymer.

6. The electronic device for performing active biological operations of claim 1 wherein the support substrate is flex circuit.

7. The electronic device for performing active biological operations of claim 1 wherein the support substrate is a circuit board.

8. The electronic device for performing active biological operations of claim 1 further includes fluidics disposed on the first surface of the support substrate.

9. The electronic device for performing active biological operations of claim 1 further includes solder bumps between the support substrate and the second substrate.

10. An electronic device for performing active biological operations, comprising:

a support substrate having a first and second surface, and a via between the first and second surfaces to permit fluid flow through the substrate,

a second substrate including at least a first surface, the first surface being adapted to be disposed in facing arrangement with the second surface of the first substrate, the second substrate including an array of microlocations disposed on the first surface of the second substrate, the array being adapted to receive said fluid,

a sealant disposed between the second face of the support substrate and the first face of the second substrate,

a source of illumination, and

an edge illumination layer having an input adapted to receive the illumination from the source, and an output adapted to direct the illumination to the array, the edge illumination layer being adhered to the second surface of the support substrate and disposed between the support substrate and the second substrate, the illumination from the output of the edge illumination layer being directed substantially parallel to the support substrate and second substrate so as to illuminate the array.

11. The electronic device for performing active biological operations of claim 10 wherein the second substrate is a chip.

12. The electronic device for performing active biological operations of claim 10 wherein the source of illumination is a laser.

13. The electronic device for performing active biological operations of claim 12 wherein the laser is a laser bar.

14. The electronic device for performing active biological operations of claim 10 wherein the edge illumination layer is a polymer layer.

15. The electronic device for performing active biological operations of claim 10 wherein the support substrate is flex circuit.

16. The electronic device for performing active biological operations of claim 10 wherein the support substrate is a circuit board.

17. The electronic device for performing active biological operations of claim 10 further including fluidics disposed on the first surface of the support substrate.

18. The electronic device for performing active biological operations of claim 10 further including solder bumps between the support substrate and this second substrate.

19. The electronic device for performing active biological operations of claim 10 wherein the edge illumination layer includes holes therein to permit electrical interconnections to pass through.

20. The electronic device for performing active biological operations of claim 10 wherein the edge illumination layer includes vias therein to permit electrical interconnections to pass through.

21. The electronic device for performing active biological operations of claim 10 wherein the edge illumination layer includes pathways therein to permit electrical interconnections to pass through.

22. The electronic device for performing active biological operations of claim 10 wherein the output of the edge illumination layer terminates outside of the sealant.

23. The electronic device for performing active biological operations of claim 10 wherein the output of the edge illumination layer terminates inside of the sealant.

24. The electronic device for performing active biological operations of claim 10 further comprising a top member adjacent to the first surface of the support substrate.

25. The electronic device for performing active biological operations of claim 24 further including an adhesive layer disposed between the first surface of the support substrate and the top member.

26. The electronic device for performing active biological operations of claim 24 wherein the top member comprises a window.

27. The electronic device for performing active biological operations of claim 24 further includes surface mounted electronic components included on the first surface of the second substrate.

28. An electronic device for performing active biological operations, comprising:

a support substrate having a first and second surface, and a via between the first and second surfaces to permit fluid flow through the substrate,

a second substrate including at least a first surface, the first surface being adapted to be disposed in facing arrangement with the second surface of the first substrate, the second substrate including an array of microlocations disposed on the first surface of the second substrate, the array being adapted to receive said fluid,

a sealant disposed between the second face of the support substrate and the first face of the second substrate,

a source of illumination, and

a waveguide having an input adapted to receive the illumination from the source, and an output which is disposed toward the first surface of the second substrate, the waveguide being adjacent to the support substrate and disposed in a region between the second surface of the support substrate and the first surface of the second substrate, the illumination from the waveguide being directed substantially parallel to the support substrate and the second substrate so as to illuminate the array.

29. The electronic device for performing active biological operations of claim 28 wherein the second substrate is a chip.

30. The electronic device for performing active biological operations of claim 28 wherein the source of illumination is a laser.

31. The electronic device for performing active biological operations of claim 30 wherein the laser is a laser bar.

32. The electronic device for performing active biological operations of claim 28 wherein the waveguide comprises a polymer.

33. The electronic device for performing active biological operations of claim 28 wherein the support substrate is a flex circuit.

34. The electronic device for performing active biological operations of claim 28 wherein the support substrate is a circuit board.

35. The electronic device for performing active biological operations of claim 28 further including fluidics disposed on the first surface of the support substrate.

36. The electronic device for performing active biological operations of claim 28 further comprising a top member adjacent to the first surface of the support substrate.

37. The electronic device for performing active biological operations of claim 36 wherein the top member comprises a window.

38. A method of performing an assay on a sample containing charged biological material, the assay being performed by an array disposed on a surface of a substrate, the substrate disposed in a facing arrangement with a support substrate, a sealant being disposed between an interface between the substrate containing the array and the support substrate, the support substrate including a via therethrough to permit fluid flow from an assay chamber disposed atop the support substrate down to the array, the method comprising the steps of:

loading a sample chamber with the sample containing charged biological material;

performing at least one processing function within the sample loading chamber;

transporting at least a portion of the charged biological materials in the sample chamber to the assay chamber, wherein the charged biological material flows down through the via onto the array;

illuminating the array with a waveguide, the waveguide having an input adapted to receive illumination from a source and an output which is disposed toward the array, the waveguide being adjacent to the support substrate and disposed between the support substrate and the second substrate, the illumination from the output of the waveguide being directed substantially parallel to the support substrate and the second substrate so as to illuminate the array; and

optically accessing the array down through the via.