Nanostructured separation and analysis devices for biological membranes

Abstract

The present invention provides a nanostructured device comprising a substrate including nanotroughs therein; and a lipid bilayer suspended on or supported in the substrate. A separation method is also provided comprising the steps of supporting or suspending a lipid bilayer on a substrate; wherein the substrate comprises nanostructures and wherein the lipid bilayer comprises at least one membrane associated biomolecule; and applying a driving force to the lipid bilayer to separate the membrane associated biomolecule from the lipid bilayer and to drive the membrane associated biomolecule into the nanostructures.

1. A nanostructured device comprising:
 a substrate including at least one nanotrough therein; and    a lipid bilayer suspended over said at least one nanotrough.    
     
     
       2. The nanostructured device of  claim 1 , wherein said lipid bilayer comprises a simple bilayer. 
     
     
       3. The nanostructured device of  claim 1 , wherein said lipid bilayer comprises a hybrid bilayer. 
     
     
       4. The nanostructured device of  claim 3 , wherein said hybrid bilayer comprises a self-assembled monolayer hybrid bilayer. 
     
     
       5. The nanostructured device of  claim 1 , wherein said at least one nanotrough is filled with at least one fluid. 
     
     
       6. The nanostructured device of  claim 1 , wherein said nanostructured device further comprises an array of nanostructures arranged so that said array has a gradient property. 
     
     
       7. The nanostructured device of  claim 1 , wherein said nanostructured device further comprises at least one nanostructured channel. 
     
     
       8. The nanostructured device of  claim 1 , wherein said substrate comprises Si. 
     
     
       9. The nanostructured device of  claim 1 , wherein said substrate comprises a semiconductor chip. 
     
     
       10. The nanostructured device of  claim 1 , wherein said nanostructured device comprises a biochip. 
     
     
       11. A nanostructured device comprising:
 a substrate including at least one nanotrough therein; and    at least one lipid bilayer supported in at least one of said at least one nanotroughs so as to allow biomolecules to pass from said at least one lipid bilayer into said at least one respective nanotrough.    
     
     
       12. The nanostructured device of  claim 11 , wherein said lipid bilayer comprises a simple bilayer. 
     
     
       13. The nanostructured device of  claim 11 , wherein said lipid bilayer comprises a hybrid bilayer. 
     
     
       14. The nanostructured device of  claim 13 , wherein said hybrid bilayer comprises a self-assembled monolayer hybrid bilayer. 
     
     
       15. The nanostructured device of  claim 11 , wherein said nanostructured device further comprises an array of nanostructures arranged so that said array has a gradient property. 
     
     
       16. The nanostructured device of  claim 11 , wherein said nanostructured device further comprises at least one nanostructured channel. 
     
     
       17. The nanostructured device of  claim 11 , wherein said substrate comprises Si. 
     
     
       18. The nanostructured device of  claim 11 , wherein said substrate comprises a semiconductor chip. 
     
     
       19. The nanostructured device of  claim 11 , wherein said nanostructured device comprises a biochip. 
     
     
       20. A separation method comprising the steps of:
 (a) supporting or suspending a lipid bilayer on a substrate; wherein said substrate comprises at least one nanostructure and wherein said lipid bilayer comprises at least one membrane associated biomolecule; and    (b) applying a driving force to said lipid bilayer to separate said at least one membrane associate biomolecule from said lipid bilayer and to drive said at least one membrane associated biomolecule within said lipid bilayer into said at least one nanostructure.    
     
     
       21. The method of  claim 20 , wherein said at least one nanostructure comprises at least one nanotrough. 
     
     
       22. The method of  claim 21 , wherein said at least one nanotrough is filled with at least one fluid. 
     
     
       23. The method of  claim 20 , wherein said at least one nanostructure comprises at least one channel. 
     
     
       24. The method of  claim 20 , wherein said at least one nanostructure further comprises at least on one protrusion. 
     
     
       25. The method of  claim 20 , wherein said substrate comprises Si. 
     
     
       26. The method of  claim 20 , wherein said lipid bilayer comprises a simple bilayer. 
     
     
       27. The method of  claim 20 , wherein said lipid bilayer comprises a hybrid bilayer. 
     
     
       28. The method of  claim 27 , wherein said hybrid bilayer comprises a self-assembled monolayer hybrid bilayer. 
     
     
       29. The method of  claim 20 , wherein said at least one nanostructure comprises an array of nanostructures arranged so that said array has a gradient property. 
     
     
       30. The method of  claim 20 , wherein said at least one membrane associated biomolecule comprises a transmembrane protein. 
     
     
       31. The method of  claim 20 , wherein said at least one membrane associated biomolecule comprises a membrane phospholipid. 
     
     
       32. The method of  claim 20 , wherein said at least one membrane associated biomolecule comprises a lipophilic biomolecule. 
     
     
       33. The method of  claim 20 , wherein said driving force comprises electrophoresis. 
     
     
       34. The method of  claim 20 , wherein said driving force comprises an externally applied pressure. 
     
     
       35. The method of  claim 20 , wherein said driving force comprises capillarity. 
     
     
       36. The method of  claim 20 , wherein said driving force comprises diffusion. 
     
     
       37. The method of  claim 20 , wherein said driving force comprises osmosis. 
     
     
       38. A method for separating particles comprising:
 ( a )  providing a substrate and a plurality of structures arranged on said substrate, wherein said structures comprise successive rows of protrusions, said protrusions exhibiting a gradient property across a plane of said substrate and in a direction transverse to the successive rows of protrusions, the protrusions of each row being of substantially the same size across at least a portion of the substrate; and      ( b )  flowing a plurality of said particles through said structures in said direction transverse to the successive rows of protrusions to effect separation of said plurality of particles based on affinity.     
     
     
       39. The method of  claim 38 , wherein said separation based on affinity comprises affinity chromatography. 
     
     
       40. The method of  claim 39 , wherein said separation based on affinity chromatography comprises immunoaffinity. 
     
     
       41. The method of  claim 40 , wherein said structures further comprise antibodies. 
     
     
       42. The method of  claim 39 , wherein said structures further comprise enzymes. 
     
     
       43. The method of  claim 38 , wherein said gradient is discrete. 
     
     
       44. The method of  claim 38 , wherein said substrate comprises Si. 
     
     
       45. The method of  claim 38 , wherein said substrate comprises silicon carbide. 
     
     
       46. The method of  claim 38 , wherein said particles are biomolecules. 
     
     
       47. The method of  claim 38 , wherein said structures are surface modified. 
     
     
       48. The method of  claim 47 , wherein the surface modification comprises modification with poly- ethylene glycol.   
     
     
       49. The method of  claim 47 , wherein the surface modification comprises modification with one or more oligonucleotide probes. 
     
     
       50. The method of  claim 47 , wherein the surface modification comprises modification with a hydrophobic molecular or oligomeric species. 
     
     
       51. The method of  claim 47 , wherein the surface modification comprises modification with a chiral selector selected from the group consisting of cyclodextrins, macrocyclic antibiotics and crown ethers. 
     
     
       52. The method of  claim 38 , wherein separating particles further comprises applying a driving force to induce said flowing of particles. 
     
     
       53. The method of  claim 52 , wherein said driving force comprises externally applied pressure. 
     
     
       54. The method of  claim 52 , wherein said driving force comprises capillarity. 
     
     
       55. The method of  claim 52 , wherein said driving force comprises diffusion. 
     
     
       56. The method of  claim 54 , wherein said driving force comprises osmosis. 
     
     
       57. The method of  claim 38 , wherein said gradient property comprises a gradation in protrusion size. 
     
     
       58. The method of  claim 38 , wherein adjacent protusions in said rows define respective channels or gaps, said gradient property comprising a gradation in channel or gap size. 
     
     
       59. The method of  claim 38 , wherein protrusions in least one row are of substantially the same size as protrusions in at least one respectively adjacent row. 
     
     
       60. A method for separating particles comprising:
 ( a )  providing a substrate and a plurality of structures arranged on said substrate, wherein said structures comprise successive rows of protrusions and channels or gaps between the protrusions, the protrusions exhibiting a gradient property across a plane of said substrate and in a direction transverse to the successive rows of protrusions, the channels or gaps exhibiting a gradient property across a plane of said substrate and in a direction transverse to the successive rows of protrusions, the protrusions of each row being of substantially the same size across at least a portion of the substrate, the channels or gaps of each row being of substantially the same size across at least a portion of the substrate, protrusions in at least one row being of substantially the same size as protrusions in at least one respectively adjacent row, channels or gaps in at least one row being of substantially the same size as channels or gaps in at least one respectively adjacent row; and      ( b )  flowing a plurality of said particles through said structures in said direction transverse to the successive rows of protrusions to effect separation of said plurality of particles based on affinity.     
     
     
       61. The method of  claim 60 , wherein said gradient property comprises a gradation in protrusion size. 
     
     
       62. The method of  claim 60 , wherein said gradient property comprises a gradation in channel or gap size.