INTEGRATION OF EX SITU FABRICATED POROUS POLYMER MONOLITHS INTO FLUIDIC CHIPS

• US 20150321191A1
• Filed: 03/27/2015
• Published: 11/12/2015
• Est. Priority Date: 03/27/2014
• Status: Active Grant

• Current Assignee: University of Maryland
• Original Assignee: University of Maryland
• Inventors: KENDALL, Eric L., WEINHOLD, Erik, RAHMANIAN, Omid, DEVOE, Don L.
• Granted Patent: US 10,675,618 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: B01D 2253/342 Monoliths
• CPC Class Codes: B01J 19/2485 Monolithic reactors
• CPC Class Codes: B01J 20/3007 Moulding, shaping or extruding
• CPC Class Codes: B01J 20/3242 Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
• CPC Class Codes: B01J 20/3255 comprising a cyclic structure containing at least one of the heteroatoms nitrogen, oxygen or sulfur, e.g. heterocyclic or heteroaromatic structures
• CPC Class Codes: B01J 2219/2402 Monolithic-type reactors
• CPC Class Codes: B01J 2219/2433 of the monoliths
• CPC Class Codes: B01J 2220/82 Shaped bodies, e.g. monoliths, plugs, tubes, continuous beds
• CPC Class Codes: B01L 2200/0631 Purification arrangements, e.g. solid phase extraction [SPE]
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2300/16 Surface properties and coatings
• CPC Class Codes: B01L 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: B01L 3/5023 with a sample being transported to, and subsequently stored in an absorbent for analysis
• 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 3/502723 characterised by venting arrangements
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: C08F 220/325 containing glycidyl radical, e.g. glycidyl (meth)acrylate
• CPC Class Codes: C08F 222/102 of dialcohols, e.g. ethylene glycol di(meth)acrylate or 1,4-butanediol dimethacrylate
• CPC Class Codes: C08F 222/103 of trialcohols, e.g. trimethylolpropane tri(meth)acrylate
• CPC Class Codes: C08J 2201/026 : Crosslinking before of after foaming
• CPC Class Codes: C08J 2205/022 : Hydrogel, i.e. a gel containing an aqueous composition
• CPC Class Codes: C08J 2205/024 : Organogel, i.e. a gel containing an organic composition
• CPC Class Codes: C08J 2207/00 : Foams characterised by their intended use
• CPC Class Codes: C08J 2333/10 : Homopolymers or copolymers of methacrylic acid esters
• CPC Class Codes: C08J 2333/14 : of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
• CPC Class Codes: C08J 2335/02 : Characterised by the use of homopolymers or copolymers of esters C08J2335/06, C08J2335/08 take precedence
• CPC Class Codes: C08J 3/246 : Intercrosslinking of at least two polymers
• CPC Class Codes: C08J 9/224 : Surface treatment
• CPC Class Codes: C08J 9/286 : the liquid phase being a solvent for the monomers but not for the resulting macromolecular composition, i.e. macroporous or macroreticular polymers
• CPC Class Codes: C08J 9/36 : After-treatment C08J9/22 takes precedence

Abstract

Bare porous polymer monoliths, fluidic chips, methods of incorporating bare porous polymer monoliths into fluidic chips, and methods for functionalizing bare porous polymer monoliths are described. Bare porous polymer monoliths may be fabricated ex situ in a mold. The bare porous polymer monoliths may also be functionalized ex situ. Incorporating the bare preformed porous polymer monoliths into the fluidic chips may include inserting the monoliths into channels of channel substrates of the fluidic chips. Incorporating the bare preformed porous polymer monoliths into the fluidic chips may include bonding a capping layer to the channel substrate. The bare porous polymer monoliths may be mechanically anchored to channel walls and to the capping layer. The bare porous polymer monoliths may be functionalized by ex situ immobilization of capture probes on the monoliths. The monoliths may be functionalized by direct attachment of chitosan.

Claims

1. A method of incorporating one or more porous polymer monoliths into a fluidic chip, the method comprising:

inserting one or more bare preformed porous polymer monoliths into one or more channels of a channel substrate of the fluidic chip.

2. The method of claim 1, further comprising fabricating the one or more bare porous polymer monoliths.

3. The method of claim 2, wherein fabricating the one or more bare porous polymer monoliths comprises fabricating one or more porous polymer monoliths in a mold.

4. The method of claim 3, wherein fabricating the one or more monoliths in the mold comprises:

adding a pre-monolith solution to one or more channels of a molding substrate;

photopolymerizing the pre-monolith solution; and

removing the polymerized solution from the one or more channels of the molding substrate.

5. The method of claim 1, further comprising chemically functionalizing one or more porous polymer monoliths, wherein the one or more inserted monoliths comprise the one or more functionalized porous polymer monoliths.

6. The method of claim 5, wherein chemically functionalizing one or more porous polymer monoliths comprises immobilizing a capture probe on the one or more porous polymer monoliths.

7. The method of claim 6, wherein the capture probe is an antibody, protein, amino acid, or peptide.

8. The method of claim 6, wherein the capture probe is labeled with a fluorescent marker.

9. The method of claim 6, wherein the capture probe is chitosan.

10. The method of claim 9, wherein the chitosan is immobilized on the one or more porous polymer monoliths using a bifunctional cross-linker.

11. The method of claim 9, wherein the chitosan is immobilized on the one or more porous polymer monoliths through a direct reaction of the chitosan with the one or more porous polymer monoliths.

12. The method of claim 1, further comprising bonding a capping layer to the channel substrate of the fluidic chip, wherein bonding the capping layer to the channel substrate seals the one or more bare porous polymer monoliths in the one or more channels of the channel substrate of the fluidic chip.

13. The method of claim 1, wherein inserting the one or more monoliths into one or more channels of the channel substrate comprises:

depositing a bare porous polymer monolith within a droplet of water onto the channel substrate; and

seating the deposited monolith into a channel of the channel substrate.

14. The method of claim 13, further comprising:

suspending a bare porous polymer monolith in water; and

drawing the suspended monolith into a pipette;

wherein the monolith deposited onto the channel substrate is deposited from the pipette.

15. The method of claim 13, further comprising:

removing the water droplet from the channel substrate; and

drying the channel substrate.

16. The method of claim 13, wherein seating the deposited monolith into the channel comprises agitating the deposited monolith.

17. The method of claim 1, wherein the one or more monoliths have cross-sectional dimensions larger than the cross-sectional dimensions of the one or more channels.

18. The method of claim 1, wherein the one or more monoliths are oversized relative to the one or more channels.

19. The method of claim 1, wherein inserting the one or more bare porous polymer monoliths into the one or more channels of the channel substrate of the fluidic chip comprises:

inserting a first bare porous polymer monolith in a channel of the one or more channels of the channel substrate; and

inserting a second bare porous polymer monolith in the channel of the one or more channels of the channel substrate.

20. The method of claim 19, wherein the first monolith has a first functionalization, the second monolith has a second functionalization, and the first functionalization is different than the second functionalization.

21. The method of claim 20, wherein the first monolith comprises a first monolith chemistry, the second monolith comprises a second monolith chemistry, and the first monolith chemistry and the second monolith chemistry are different.

22. The method of claim 21, wherein the first monolith chemistry is hydrophilic, and the second monolith chemistry is hydrophobic.

23. The method of claim 1, further comprising anchoring the one or more inserted monoliths to walls of the one or more channels.

24. The method of claim 23, wherein anchoring the one or more inserted monoliths comprises softening the one or more channels of the channel substrate of the fluidic chip.

25. The method of claim 24, wherein softening the one or more channels of the channel substrate of the fluidic chip comprises exposing at least a portion of the one or more channels to a solvent.

26. The method of claim 25, wherein the solvent comprises decahydronaphthalene (decalin).

27. The method of claim 26, wherein the solvent comprises a solution of decalin in ethanol.

28. The method of claim 23, wherein anchoring the one or more inserted monoliths to the walls of the one or more channels results in mechanical interlocking of the one or more inserted monoliths and the walls of the one or more channels.

29. The method of claim 23, wherein anchoring the one or more inserted monoliths to the walls of the one or more channels does not result in covalent attachment of the one or more inserted monoliths and the walls of the one or more channels.

30. A fluidic chip comprising:

a channel substrate including one or more channels;

one or more bare porous polymer monoliths mechanically anchored to walls of the one or more channels of the channel substrate.

31. The fluidic chip of claim 30, wherein the one or more mechanically anchored bare porous polymer monoliths comprises one or more chemically functionalized porous polymer monoliths.

32. The fluidic chip of claim 31, wherein the one or more chemically functionalized porous polymer monoliths comprise immobilized capture probes.

33. The fluidic chip of claim 32, wherein the immobilized capture probes comprise antibodies, proteins, aptamers, amino acids, peptides, or synthetic capture probes.

34. The fluidic chip of claim 32, wherein the immobilized capture probes are labeled with fluorescent markers.

35. The fluidic chip of claim 32, wherein the immobilized capture probes are chitosan.

36. The fluidic chip of claim 35, wherein the chitosan is immobilized on one or more porous polymer monoliths using a bifunctional cross-linker.

37. The fluidic chip of claim 35, wherein the chitosan is immobilized through a direct reaction of the chitosan with one or more porous polymer monoliths.

38. The fluidic chip of claim 30, further comprising a capping layer bonded to the channel substrate, wherein the one or more monoliths are sealed within the one or more channels of the channel substrate between the channel substrate and the capping layer.

39. The fluidic chip of claim 30, wherein the channel substrate is a thermoplastic substrate.

40. The fluidic chip of claim 30, wherein the channel substrate comprises cyclic olefin copolymer.

41. The fluidic chip of claim 30, wherein the one or more channels of the channel substrate have a triangular or trapezoidal cross-section.

42. The fluidic chip of claim 30, wherein the one or more monoliths have a triangular or trapezoidal cross-section.

43. The fluidic chip of claim 30, wherein the one or more monoliths have cross-sectional dimensions larger than the cross-sectional dimensions of the one or more channels.

44. The fluidic chip of claim 30, wherein the one or more monoliths are oversized relative to the one or more channels.

45. The fluidic chip of claim 30, wherein the one or more bare porous polymer monoliths comprise:

a first monolith in a channel of the one or more channels of the channel substrate; and

a second monolith in the channel of the one or more channels of the channel substrate.

46. The fluidic chip of claim 45, wherein the first monolith has a first functionalization, the second monolith has a second functionalization, and the first functionalization is different than the second functionalization.

47. The fluidic chip of claim 46, wherein the first and second monoliths are functionalized with different fluorescent markers.

48. The fluidic chip of claim 45, wherein the first monolith comprises a first monolith chemistry, the second monolith comprises a second monolith chemistry, and the first monolith chemistry and the second monolith chemistry are different.

49. The fluidic chip of claim 48, wherein the first monolith chemistry is hydrophilic, and the second monolith chemistry is hydrophobic.

50. The fluidic chip of claim 45, wherein the first monolith is un-functionalized, and the second monolith is functionalized.

51. The fluidic chip of claim 50, wherein the one or more bare porous polymer monoliths further comprise a third monolith in the channel of the one or more channels of the channel substrate, the second monolith is functionalized with covalently-attached immunoglobin-binding protein, and the third monolith is functionalized with a covalently-attached fluorescent marker and immunoglobin conjugate.

52. The fluidic chip of claim 30, wherein:

the one or more channels of the channel substrate comprise an inlet of a T-junction, a first downstream branch of the T-junction, and a second downstream branch of the T-junction;

the one or more bare porous polymer monoliths comprise first and second monoliths;

the first monolith is in the first downstream branch of the T-junction, is adjacent to the inlet of the T-junction, and comprises a hydrophobic monolith chemistry; and

the second monolith is in the second downstream branch of the T-junction, is adjacent to the inlet of the T-junction, and comprises a hydrophilic monolith chemistry.

53. The fluidic chip of claim 52, wherein the first monolith comprises butylmethacylate, and the second monolith comprises glycidyl methacrylate.

54. The fluidic chip of claim 30, wherein the one or more channels have one or more of a width and a height within a range greater than or equal to 10 micrometers and less than or equal to 1 centimeter.

55. The fluidic chip of claim 54, wherein the one or more channels have one or more of a width and a height within a range greater than or equal to 1 millimeter and less than or equal to 1 centimeter.

56. The fluidic chip of claim 54, wherein the one or more channels have one or more of a width and a height within a range greater than or equal to 100 micrometers and less than or equal to 1 millimeter.

57. The fluidic chip of claim 54, wherein the one or more channels have one or more of a width and a height within a range greater than or equal to 10 micrometer and less than or equal to 100 micrometers.

58. The fluidic chip of claim 30, wherein the one or more monoliths have a length within a range greater than or equal to 10 micrometers and less than or equal to 1 centimeter.

59. The fluidic chip of claim 58, wherein the one or more monoliths have a length within a range greater than or equal to 1 millimeter and less than or equal to 1 centimeter.

60. The fluidic chip of claim 58, wherein the one or more monoliths have a length within a range greater than or equal to 100 micrometers and less than or equal to 1 millimeter.

61. The fluidic chip of claim 58, wherein the one or more monoliths have a length within a range greater than or equal to 10 micrometer and less than or equal to 100 micrometers.

62. A chitosan-functionalized porous polymer monolith comprising:

a porous polymer monolith; and

a chitosan anchored to the porous polymer monolith.

63. The monolith of claim 62, wherein the chitosan is anchored to the porous polymer monolith using a bifunctional cross-linker.

64. The monolith of claim 63, wherein the bifunctional cross-linker is N-[γ

-maleimidobutyryloxy]succinimide ester.

65. The monolith of claim 62, wherein the chitosan is anchored to the porous polymer monolith through a direct reaction of the chitosan with the porous polymer monolith.

66. The monolith of claim 62, wherein the porous polymer monolith comprises glycidyl methacrylate.

67. A method for manufacturing a chitosan-functionalized porous polymer monolith, the method comprising:

anchoring chitosan to a porous polymer monolith.

68. The method of claim 67, wherein anchoring the chitosan comprises using a bifunctional cross-linker to couple amines from the chitosan with epoxy groups on the porous polymer monolith.

69. The method of claim 68, wherein the bifunctional cross-linker is N-[γ

-maleimidobutyryloxy]succinimide ester.

70. The method of claim 67, wherein the anchoring the chitosan comprises directly attaching chitosan on the porous polymer monolith through a direct reaction of the chitosan with the porous polymer monolith.