Device and method for multiple analyte detection

• US 8,062,883 B2
• Filed: 01/09/2007
• Issued: 11/22/2011
• Est. Priority Date: 04/03/1996
• Status: Expired due to Fees

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Woudenberg, Timothy, Kowallis, Reid B., Albin, Michael, Winn-Deen, Emily S., Ragusa, Robert P., Raysberg, Yefim
• Primary Examiner(s): CHIN, CHRISTOPHER L
• Application Number:
  US11/651,317
• Publication Number:
  US 20070134710A1
• Time in Patent Office: 1,778 Days
• Field of Search: None
• US Class Current: 435/287.2
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00599 Solution-phase processes
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 2400/049 vacuum
• 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 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50851 specially adapted for heating or cooling samples laboratory heating apparatus B01L7/00; incubators C12M
• 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: C12Q 1/08 using multifield media
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 2565/631 being a biochannel or pore
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 50/08 Liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase or in solution during library creation; Particular methods of cleavage from the liquid support
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 2035/00148 Test cards, e.g. Biomerieux or McDonnel multiwell test cards
• CPC Class Codes: G01N 21/6452 : Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: Y10S 436/805 : Optical property
• CPC Class Codes: Y10S 436/807 : Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10S 436/808 : Automated or kit
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/25 : including sample preparation

Abstract

The invention is directed to a method and device for simultaneously testing a sample for the presence, absence, and/or amounts of one or more a plurality of selected analytes. The invention includes, in one aspect, a device for detecting or quantitating a plurality of different analytes in a liquid sample. The device includes a substrate which defines a sample-distribution network having (i) a sample inlet, (ii) one or more detection chambers, and (iii) channel means providing a dead-end fluid connection between each of the chambers and the inlet Each chamber may include an analyte-specific reagent effective to react with a selected analyte that may be present in the sample, and detection means for detecting the signal. Also disclosed are methods utilizing the device.

Claims

1. A device comprising:

a substrate;

a sample-distribution network defined by the substrate and comprising (i) a sample inlet, (ii) two or more detection chambers, and (iii) a fluid communication between the two or more detection chambers and the inlet; and

non-immobilized detection reagents pre-loaded in each of the two or more detection chambers, the detection reagents comprising a first oligonucleotide, a second oligonucleotide, and a detection reagent capable of producing an optical signal;

wherein the fluid communication comprises a channel and respective fluid connections connecting the channel to the respective detection chambers of the two or more detection chambers, and the fluid connections branch off from opposite sides of the channel.

2. The device of claim 1, wherein the fluid connections branch off in a staggered manner from opposite sides of the channel.

3. The device of claim 2, wherein each fluid connection comprises an L-shaped configuration.

4. The device of claim 1, wherein the fluid connections branch off in pairs of opposing fluid connections on opposite sides of the channel.

5. The device of claim 4, wherein each fluid connection comprises an L-shaped configuration.

6. The device of claim 1, wherein the detection reagents have been dried down in the two or more detection chambers.

7. The device of claim 1, wherein the first oligonucleotide is effective to selectively bind to a target polynucleotide having a defined sequence.

8. The device of claim 1, wherein the first oligonucleotide and the second oligonucleotide comprise an oligonucleotide primer pair suitable for amplifying, by polymerase chain reaction, a selected target polynucleotide region.

9. The device of claim 1, wherein the substrate comprises a copolymer material.

10. The device of claim 1, wherein the substrate further comprises a high thermal conductivity metal surface.

11. The device of claim 10, wherein the high thermal conductivity metal surface comprises copper.

12. The device of claim 10, wherein the high thermal conductivity metal surface comprises aluminum.

13. The device of claim 10, further comprising means for modulating the temperature of the two or more detection chambers, in the substrate.

14. The device of claim 1, further comprising an optically clear cover layer disposed over the sample distribution network.

15. The device of claim 1, wherein the detection reagent capable of producing an optical signal comprises a fluorescently detectable detection reagent.

16. The device of claim 1, wherein the substrate defines at least two such sample-distribution networks.

17. The device of claim 1, further comprising means for modulating the temperature of the two or more detection chambers, in the substrate.

18. The device of claim 1, wherein the substrate comprises two or more layers.

19. The device of claim 18, wherein the two or more layers are laminated together.

20. The device of claim 18, wherein the two or more layers comprise at least one silicon layer.

21. The device of claim 20, further comprising an oxidation layer coated on the at least one silicon layer, wherein each of the two or more detection chambers is at least partially defined by the oxidation layer and the oxidation layer separates the at least one silicon layer from each of the two or more detection chambers.

22. A system comprising the device of claim 1 and an external temperature controller.

23. The device of claim 1, wherein the fluid communication comprises a sample delivery channel, and the device further comprises a plurality of dead-end fluid connections, wherein each of the dead-end fluid connections provides a dead-end communication between a respective one of the two or more detection chambers and the sample delivery channel.

24. A device comprising:

a substrate;

a sample-distribution network defined by the substrate and comprising (i) a sample inlet, (ii) two or more detection chambers, and (iii) a fluid communication between the two or more detection chambers and the inlet; and

detection reagents pre-loaded in each of the two or more detection chambers;

wherein the fluid communication comprises a channel and respective fluid connections connecting the channel to the respective detection chambers of the two or more detection chambers, the fluid connections branch off from opposite sides of the channel, the fluid communication comprises a sample delivery channel, and the device further comprises a plurality of dead-end fluid connections, wherein each of the dead-end fluid connections provides a dead-end communication between a respective one of the two or more detection chambers and the sample delivery channel.

25. The device of claim 24, wherein the fluid connections branch off in a staggered manner from opposite sides of the channel.

26. The device of claim 25, wherein each fluid connection comprises an L-shaped configuration.

27. The device of claim 25, wherein the fluid connections branch off in pairs of opposing fluid connections on opposite sides of the channel.

28. The device of claim 27, wherein each fluid connection comprises an L-shaped configuration.

29. The device of claim 24, wherein the detection reagents have been dried down in the two or more detection chambers.

30. The device of claim 24, wherein the detection reagents comprise a sequence-selective reagent.

31. The device of claim 30, wherein the sequence-selective reagent comprises a polynucleotide effective to selectively bind to a target polynucleotide having a defined sequence.

32. The device of claim 24, wherein the detection reagents comprise an oligonucleotide primer pair suitable for amplifying, by polymerase chain reaction, a selected target polynucleotide region.

33. The device of claim 24, wherein the substrate comprises a copolymer material.

34. The device of claim 24, wherein the substrate further comprises a high thermal conductivity metal surface.

35. The device of claim 34, wherein the high thermal conductivity metal surface comprises copper.

36. The device of claim 34, wherein the high thermal conductivity metal surface comprises aluminum.

37. The device of claim 34, further comprising means for modulating the temperature of the two or more detection chambers, in the substrate.

38. The device of claim 24, further comprising an optically clear cover layer disposed over the sample distribution network.

39. The device of claim 24, wherein the detection reagents comprise fluorescently detectable detection reagents.

40. The device of claim 24, wherein the substrate defines at least two such sample-distribution networks.

41. The device of claim 24, further comprising means for modulating the temperature of the two or more detection chambers, in the substrate.

42. The device of claim 24, wherein the substrate comprises two or more layers.

43. The device of claim 42, wherein the two or more layers are laminated together.

44. The device of claim 42, wherein the two or more layers comprise at least one silicon layer.

45. The device of claim 44, further comprising an oxidation layer coated on the at least one silicon layer, wherein each of the two or more detection chambers is at least partially defined by the oxidation layer and the oxidation layer separates the at least one silicon layer from each of the two or more detection chambers.