Bioarray chip reaction apparatus and its manufacture

• US 6,399,365 B2
• Filed: 07/17/2001
• Issued: 06/04/2002
• Est. Priority Date: 06/08/1994
• Status: Expired due to Term

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Winkler, James L., Goss, Virginia W., Besemer, Donald M.
• Primary Examiner(s): Siew, Jeffrey
• Application Number:
  US09/907,196
• Publication Number:
  US 20010041341A1
• Time in Patent Office: 322 Days
• Field of Search: 435/6, 435/7.1, 435/91.1, 435/91.2, 435/285.1, 435/287.2, 536/22.1, 536/23.1, 536/24.3, 536/24.31, 536/24.32, 536/24.33
• US Class Current: 435/287.2
• CPC Class Codes: B01F 33/252 using bubbles as loose mixing element
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/40 Mixers using gas or liquid agitation, e.g. with air supply tubes
• CPC Class Codes: B01F 33/45 Magnetic mixers; Mixers with magnetically driven stirrers
• CPC Class Codes: B01F 33/452 using independent floating stirring elements
• 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 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00371 comprising electrodes
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00531 essentially square
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00547 Bar codes
• 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 2219/00608 : DNA chips
• CPC Class Codes: B01J 2219/0061 : The surface being organic
• CPC Class Codes: B01J 2219/00612 : the surface being inorganic
• CPC Class Codes: B01J 2219/00621 : 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 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00662 : Two-dimensional arrays within two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00695 : Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00711 : Light-directed synthesis
• 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 2200/027 : for microfluidic devices
• CPC Class Codes: B01L 2200/0689 : Sealing
• CPC Class Codes: B01L 2200/12 : Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/147 : Employing temperature sensors
• CPC Class Codes: B01L 2300/0636 : Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0816 : Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0819 : Microarrays; Biochips
• CPC Class Codes: B01L 2300/0825 : Test strips
• CPC Class Codes: B01L 2300/0877 : Flow chambers
• CPC Class Codes: B01L 2300/1805 : Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
• CPC Class Codes: B01L 2400/0439 : ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0442 : thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 2400/0487 : fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0611 : duck bill valves
• CPC Class Codes: B01L 2400/065 : sliding valves
• CPC Class Codes: B01L 3/5027 : by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• 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 9/52 : Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• 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: 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: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: H01L 21/67144 : Apparatus for mounting on conductive members, e.g. leadframes or conductors on insulating substrates
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

A package for hybridization includes a substrate and a housing. The substrate has a first surface that includes an array of probes having biological polymers immobilized thereon. The housing includes a fluid cavity constructed and arranged for hybridization of a target to a probe of the probe array located inside the fluid cavity. The housing also includes a bar code.

Claims

1. A package for hybridization, comprising:

a substrate comprising a first surface including a probe array with different probes comprising biological polymers immobilized on said first surface;

said probe array including a density exceeding 100 different biological polymers per cm²; and

a housing including a fluid cavity constructed and arranged for hybridization of a target to a probe of said probe array, said housing including a bar code.

6. The package of claim 1, wherein said housing includes an alignment structure arranged for alignment of said probe array with respect to a detection system.

17. The package of claim 1, 2, 8 or 10, wherein said biological polymers include nucleic acids.

18. The package of claim 17, wherein said nucleic acids are attached to said surface through a linker group.

19. The package of claim 18, wherein said nucleic acids are from 4 to 20 nucleotides in length.

20. The package of claim 1, 2, 8 or 10, wherein each of said polymers are separately located within an area of about 1 μ

m² to about 1000 μ

m².

21. The package of claim 20, wherein said nucleic acids have a density exceeding 400 different nucleic acids per cm².

22. The package of claim 20, wherein said nucleic acids have a density exceeding 1000 different nucleic acids per cm².

23. The package of claim 1, 2, 8 or 10, wherein said biological polymers are attached to said substrate by selectively illuminating said substrate.

24. The package of claim 1, 2, 8 or 10, wherein said biological polymers include oligonucleotides.

25. The package of claim 1, 2, 8 or 10, wherein said biological polymers include proteins or polypeptides.

26. The package of claim 1, 2, 8 or 10, wherein said biological polymers are selected from the group consisting of:

agonists and antagonists for cell membrane receptor, toxins, venoms, viral epitopes, hormones, hormone receptors, enzymes, enzyme substrates, cofactors, drugs, lectins, sugars, oligosaccharides, and monoclonal antibodies.

27. The package of claim 1, wherein said nucleic acids have a density exceeding 400 different nucleic acids per cm².

28. The package of claim 1, wherein said nucleic acids have a density exceeding 1000 different nucleic acids per cm².

33. The package of claim 1, 2 or 10 wherein said biological polymers are covalently attached to said surface.

2. A package for hybridization, comprising:

an optically transparent chip comprising a first surface including an array of probes comprising biological polymers immobilized on said first surface; and

a housing including a fluid cavity constructed and arranged for hybridization of a target to a probe of said probe array located inside said fluid cavity, said housing including a bar code and being arranged for use with a detection system.

3. The package of claim 2, wherein said detection system is constructed and arranged for scanning said probe array, said probe array being located inside said fluid cavity.

4. The package of claim 2, wherein said housing includes an alignment structure arranged for alignment of said probe array with respect to said detection system.

5. The package of claim 2, wherein said detection system is constructed to detect fluorescent light emitted from said array and transmitted through said optically transparent chip and outside said package, said detected fluorescent light being used to quantitatively analyze said hybridization between said probe and target.

7. A probe array deposited on a substrate, comprising:

a probe array including different probes comprising biological polymers immobilized on said substrate and having a density exceeding 100 different biological polymers per cm², and

a bar code.

8. The probe array of claim 7, wherein said bar code is located on a housing forming a package constructed to accommodate said substrate and including an alignment structure being arranged for use with a detection system.

9. The probe array of claim 8, wherein said alignment structure is constructed to predefine a position of said probe array with respect to said detection system.

34. The array of claim 7 wherein said biological polymers are covalently attached to the substrate.

35. The array of claim 7, wherein said biological polymers have a density exceeding 400 different nucleic acids per cm².

36. The array of claim 7, wherein said biological polymers have a density exceeding 1000 different nucleic acids per cm².

37. The array of claim 7, wherein said biological polymers include nucleic acids.

38. The array of claim 7, wherein said biological polymers include proteins or polypeptides.

39. The array of claim 7, wherein said biological polymers are selected from the group consisting of:

agonists and antagonists for cell membrane receptor, toxins, venoms, viral epitopes, hormones, hormone receptors, enzymes, enzyme substrates, cofactors, drugs, lectins, sugars, oligosaccharides, and monoclonal antibodies.

40. The array of claim 7 wherein said substrate is optically transparent.

10. A package for supporting a probe array, comprising:

an optically transparent chip comprising an array of different probes including biological polymers, immobilized on a surface of said chip;

a housing constructed to receive said chip; and

a bar code associated with said chip.

11. The package of claim of claim 10, wherein said housing including a cavity constructed to receive said array of probes enclosed therein.

12. The package of claim 11, wherein said housing includes an alignment structure arranged for use with a detection system.

13. The package of claim 12, wherein said detection system is constructed and arranged to scan said probe array located inside said housing.

14. The package of claim 12, wherein said detection system is constructed and arranged for scanning said probe array to quantitatively analyze hybridization between said probes and various targets.

15. The package of claim 14, wherein said housing is constructed for introduction of fluid to contact said probe array and to hybridize said probes to targets delivered by said fluid.

16. The package of claim 11, wherein said housing includes an alignment structure arranged for use with a detection system;

said detection system being constructed to detect fluorescent light emitted from said array and transmitted through said chip.

29. The package of claim 10 wherein said biological polymers are in fluid communication.

30. The package of claim 10 wherein said biological polymers are separately located within an area of less than 10⁻

2 cm².

31. The package of claim 10 wherein there are more than 100 different sequences in the array.

32. The package of claim 10 wherein there are more than 1000 different sequences in the array.

41. A method of using a probe array, comprising:

providing an array of probes, comprising biological polymers immobilized on a substrate, having a density exceeding 100 different polymers per cm²;

providing a bar code associated with said probe array;

reading said bar code;

aligning said probe array with a detection system; and

detecting a signal from said probe array.

42. The method of using a probe array according to claim 41, wherein said nucleic acids have a density exceeding 400 different polymers per cm².

43. The method of using a probe array according to claim 41, wherein said polymers have a density exceeding 1000 different nucleic acids per cm².

44. The method of using a probe array according to claim 41, wherein said detecting said signal includes detecting a fluorescent signal emitted from said probe array.

45. The method of using a probe array according to claim 41, wherein said detecting said signal comprises scanning said probe array to quantitatively analyze said hybridization between said probes and targets.

46. The method of using a probe array according to claim 41, wherein said providing said probe array includes selectively illuminating said substrate to attach said biological polymers.

55. The method of using a probe array according to claim 41 or 47, wherein said biological polymers include nucleic acids.

56. The method of using a probe array according to claim 41 or 47, wherein said biological polymers include proteins or polypeptides.

57. The method of using a probe array according to claim 41 or 47, wherein said biological polymers are selected from the group consisting of:

agonists and antagonists for cell membrane receptor, toxins, venoms, viral epitopes, hormones, hormone receptors, enzymes, enzyme substrates, cofactors, drugs, lectins, sugars, oligosaccharides, and monoclonal antibodies.

58. The method of claims 41 or 47 wherein said reading step occurs either before or after either of said aligning and detecting steps.

47. A method of using a probe array, comprising:

providing an optically transparent chip comprising a probe array including biological polymers immobilized on a surface and at least some of said polymers hybridized to a target;

providing a housing, including an alignment structure, said housing being constructed to accommodate said chip and a bar code;

reading said bar code;

aligning said housing with a detection system using said alignment structure; and

detecting a signal from said probe array.

48. The method of using a probe array according to claim 47, wherein said housing is constructed to receive said chip to form a fluid cavity having said probe array located therein.

49. The method of using a probe array according to claim 48, wherein said detecting said signal includes detecting a fluorescent signal emitted from said probe array and transmitted through said chip to a detection system.

50. The method of using a probe array according to claim 47, wherein said housing includes a fluid cavity and said providing said probe array includes hybridizing said probes to said targets by introducing hybridization fluid inside said fluid cavity.

51. The method of using a probe array according to claim 50 further including controlling temperature of said introduced hybridization fluid.

52. The method of using a probe array according to claim 50 further including circulating said hybridization fluid during said hybridization.

53. The method of using a probe array according to claim 47, wherein said nucleic acids have a density exceeding 400 different nucleic acids per cm².

54. The method of using a probe array according to claim 47, wherein said nucleic acids have a density exceeding 1000 different nucleic acids per cm².