Nanochannel arrays and their preparation and use for high throughput macromolecular analysis

• US 8,652,828 B2
• Filed: 10/30/2008
• Issued: 02/18/2014
• Est. Priority Date: 07/25/2001
• Status: Expired due to Term

• Current Assignee: The Trustees of Princeton University (Princeton University)
• Original Assignee: The Trustees of Princeton University (Princeton University)
• Inventors: Yu, Zhaoning, Chou, Stephen Y, Cao, Han, Austin, Robert H, Tegenfeldt, Jonas O
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US12/261,406
• Publication Number:
  US 20100029508A1
• Time in Patent Office: 1,937 Days
• Field of Search: None
• US Class Current: 435/283.1
• CPC Class Codes: B01J 2219/00274 Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
• CPC Class Codes: B01L 2200/0663 Stretching or orienting elongated molecules or particles
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0896 Nanoscaled
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• 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: B81B 1/002 Holes characterised by their shape, in either longitudinal or sectional plane
• CPC Class Codes: B81B 2201/058 Microfluidics not provided for in B81B2201/051 - B81B2201/054
• CPC Class Codes: B81B 2203/0338 Channels
• CPC Class Codes: B81C 1/00071 Channels
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 1/6869 Methods for sequencing
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 27/447 using electrophoresis
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 33/48721 : Investigating individual macromolecules, e.g. by translocation through nanopores Coulter counters in general G01N15/12; fabrication methods for nanoscale apertures B81B1/00; sequencing of nucleic acids C12Q1/68
• CPC Class Codes: Y10S 977/704 : Nucleic acids, e.g. DNA or RNA
• CPC Class Codes: Y10S 977/88 : with arrangement, process, or apparatus for testing
• CPC Class Codes: Y10S 977/883 : Fluidic self-assembly, FSA

Abstract

Nanochannel arrays that enable high-throughput macromolecular analysis are disclosed. Also disclosed are methods of preparing nanochannel arrays and nanofluidic chips. Methods of analyzing macromolecules, such as entire strands of genomic DNA, are also disclosed, as well as systems for carrying out these methods.

Claims

1. A nanochannel array, comprising:

a surface having a plurality of channels in the material of the surface, said channels having a trench width of less than about 150 nanometers and a trench depth of less than 200 nanometers;

the top of at least one channel is surmounted by, and in contact with, a sealing material to render such channel enclosed, wherein at least one end of the at least one channel is in fluid communication with at least one reservoir, and

at least two of such channels being substantially free of interconnections with one another.

2. The nanochannel array of claim 1 wherein both ends of at least some of the channels are in fluid communication with reservoirs.

3. The nanochannel array of claim 1 wherein the plurality of channels is in fluid communication with at least one sample reservoir common to at least some of the channels.

4. The nanochannel array of claim 3 wherein the plurality of channels is in fluid communication with at least one waste reservoir.

5. The nanochannel array of claim 1 wherein the channels are substantially parallel.

6. The nanochannel array of claim 1 wherein the ends of the channels are capable of admitting a macromolecule in a fluid.

7. The nanochannel array of claim 1 wherein the channels are capable of transporting a macromolecule across their length.

8. The nanochannel array of claim 1 wherein the channels are capable of transporting at least one macromolecule across the length of said channels, said macromolecule being in an elongated form.

9. The nanochannel array of claim 1 wherein the channels are capable of transporting at least one biopolymer across the length of said channels.

10. The nanochannel array of claim 9 wherein the channels are capable of transporting at least one unfolded biopolymer across the length of said channels.

11. The nanochannel array of claim 9 wherein the biopolymer is a nucleic acid.

12. The nanochannel array of claim 9 wherein the biopolymer is an unfolded nucleic acid.

13. The nanochannel array of claim 1 wherein the trench width is less than 100 nanometers.

14. The nanochannel array of claim 1 wherein the trench width is less than 75 nanometers.

15. The nanochannel array of claim 1 wherein the trench width is less than 50 nanometers.

16. The nanochannel array of claim 1 wherein the trench width is less than 25 nanometers.

17. The nanochannel array of claim 1 wherein the trench width is less than 15 nanometers.

18. The nanochannel array of claim 1 wherein the trench width is about 10 nanometers.

19. The nanochannel array of claim 1 wherein the trench depth is less than 175 nanometers.

20. The nanochannel array of claim 1 wherein the trench depth is less than 125 nanometers.

21. The nanochannel array of claim 1 wherein the trench depth is less than 75 nanometers.

22. The nanochannel array of claim 1 wherein the trench depth is less than 50 nanometers.

23. The nanochannel array of claim 1 wherein the trench depth is less than 25 nanometers.

24. The nanochannel array of claim 1 wherein the trench depth is about 15 nanometers.

25. The nanochannel array of claim 1 wherein the at least a portion of the channels are pillar structures.

26. The nanochannel array of claim 1 wherein the channel period is less than about 200 nm.

27. The nanochannel array of claim 1 wherein the material of the surface is a film adjacently supported by a second substrate.

28. The nanochannel array of claim 1 wherein the surface is a surface of a substrate and the substrate material is a conducting material.

29. The nanochannel array of claim 1 wherein the surface is a surface of a substrate and the substrate material is a semi-conducting material.

30. The nanochannel array of claim 1 wherein the surface is a surface of a substrate and the substrate material is a non-conducting material.

31. The nanochannel array of claim 1 further comprising at least one optically opaque layer adjacent to the sealing material.

32. The nanochannel array of claim 1 further comprising at least one near field slit above at least one channel.

33. The nanochannel array of claim 1 further comprising sealing material adjacent to a channel bottom.

34. The nanochannel array of claim 1 further comprising sealing material adjacent to a channel wall.

35. The nanochannel array of claim 1 wherein the length of the channels is greater than 1 millimeter.

36. The nanochannel array of claim 1 wherein the length of the channels is greater than 1 centimeter.

37. The nanochannel array of claim 1 wherein the length of the channels is greater than 5 centimeters.

38. The nanochannel array of claim 1 wherein the length of the channels is greater than 15 centimeters.

39. The nanochannel array of claim 1 wherein the length of the channels is greater than 25 centimeters.

40. The nanochannel array of claim 1 wherein the surface is a surface of a substrate and the substrate is a flexible film material.

41. A nanochannel in the material of a surface, the nanochannel comprising a trench having a width of less than about 150 nanometers and a depth of less than 200 nanometers;

wherein the top of the nanochannel is surmounted by, and in contact with, a sealing material to cover the top of the nanochannel to form a lumen, such that a fluid material is capable of flowing through the lumen.