Claims
- 1. A device for directing a liquid to an analyzer, comprising a reservoir for containing a liquid, a fluid exit for directing liquid from the device to the analyzer, and a channel for conducting liquid from the reservoir to the fluid exit, wherein the reservoir further comprises an electrode in electrical contact with the liquid in the reservoir.
- 2. The device of claim 1 wherein the device is a microfabricated device.
- 3. The device of claim 1 wherein the device is formed from a material selected from the group consisting of glass, quartz, and plastic materials.
- 4. The device of claim 3 wherein the plastic materials are selected from the group consisting of hard plastic material and soft plastic material.
- 5. The device of claim 4 wherein the hard plastic material comprises polypropylene.
- 6. The device of claim 4 wherein the soft plastic material is selected from the group consisting of polydimethylsiloxane, polyurethane, and epoxy.
- 7. The device of claim 1 wherein the reservoir is etched into the device.
- 8. The device of claim 1 wherein the reservoir is formed by molding the device.
- 9. The device of claim 1 wherein the channel is etched into the device.
- 10. The device of claim 1 wherein the channel is formed by molding the device.
- 11. The device of claim 1 further comprising a contact pad connected to the electrode by a metal line.
- 12. The device of claim 1 wherein the electrode is a metal electrode.
- 13. The device of claim 1 wherein the electrode is a gold electrode.
- 14. The device of claim 1 wherein the electrode is formed by vacuum deposition.
- 15. The device of claim 1 further comprising an adhesion layer between the device and the electrode.
- 16. The device of claim 15 wherein the adhesion layer comprises a nickel chromium film.
- 17. The device of claim 1 having a thickness of about 540 μm.
- 18. The device of claim 1 wherein the reservoir has a depth of about 30 μm.
- 19. The device of claim 1 wherein the reservoir has width of about 2 mm.
- 20. The device of claim 1 wherein the channel has a depth in the range from about 5 to about 100 μm.
- 21. The device of claim 1 wherein the channel has a width in the range from about 5 to about 100 μm.
- 22. The device of claim 1 wherein the electrode has a thickness of about 60 nm.
- 23. The device of claim 1 wherein the electrode has width of about 0.4 mm and a length of about 1.0 mm.
- 24. The device of claim 15 wherein the adhesion layer has a thickness of about 10 nm.
- 25. The device of claim of claim 11 wherein the metal line has a width of about 80 μm.
- 26. The device of claim 1 comprising at least three reservoirs.
- 27. The device of claim 26 wherein each reservoir is connected by a channel to a common channel for conducting fluid from the reservoir to the fluid exit.
- 28. The device of claim 1 further comprising a cover substantially coextensive with the upper surface of the device, wherein the cover comprises an aperture coincidental with the reservoir providing access to the reservoir.
- 29. The device of claim 26 further comprising a cover substantially coextensive with the upper surface of the device, wherein the cover comprises an aperture coincidental with each reservoir providing access to the reservoir.
- 30. The device of claim 28 wherein the cover is attachable to the device.
- 31. The device of claim 1 wherein liquid comprises an analyte.
- 32. The device of claim 31 wherein the analyte is a protein.
- 33. The device of claim 31 wherein the analyte is a peptide.
- 34. The device of claim 1 wherein the liquid comprises a protein digest.
- 35. A device for directing a liquid to a mass analyzer, wherein the device comprises a plurality of reservoirs for containing a liquid, a fluid exit for directing liquid from the device to the mass analyzer, wherein each reservoir is connected by a channel to a common channel for conducting liquid to the fluid exit, and wherein each reservoir further comprises an electrode in electrical contact with the liquid in the reservoir.
- 36. The device of claim 35 wherein the device is a microfabricated device.
- 37. The device of claim 35 wherein the device is formed from a material selected from the group consisting of glass, quartz, and plastic materials.
- 38. The device of claim 35 wherein each reservoir is etched into the device.
- 39. The device of claim 35 wherein the reservoir is formed by molding the device.
- 40. The device of claim 35 wherein each channel is etched into the device.
- 41. The device of claim 35 wherein the reservoir is formed by molding the device.
- 42. The device of claim 35 further comprising a contact pad connected to each electrode by a metal line.
- 43. The device of claim 35 comprising three reservoirs.
- 44. The device of claim 35 comprising nine reservoirs.
- 45. The device of claim 35 further comprising a cover substantially coextensive with the upper surface of the device, wherein the cover comprises an aperture coincidental with each reservoir providing reservoir access.
- 46. The device of claim 35 wherein the liquid comprises an analyte.
- 47. The device of claim 46 wherein the analyte is a protein.
- 48. The device of claim 46 wherein the analyte is a peptide.
- 49. The device of claim 35 wherein the liquid comprises a protein digest.
- 50. The device of claim 35 further comprising a solid phase for immobilizing an analyte.
- 51. A system for introducing an analyte into a mass analyzer, comprising the fluidic device of claim 1, an electrospray ionization source, and a capillary for communicating a liquid from the device to the electrospray ionization source.
- 52. The system of claim 51 wherein the fluidic device comprises a plurality of reservoirs.
- 53. The system of claim 51 wherein the electrospray ionization source is a microelectrospray ionization source.
- 54. The system of claim 51 wherein the capillary comprises a fused silica capillary.
- 55. The system of claim 51 wherein the mass analyzer is a tandem mass spectrometer.
- 56. The system of claim 51 wherein the mass spectrometer is an ion trap mass spectrometer.
- 57. The system of claim 51 further comprising a computer, an array of high voltage relays, and a mass analyzer, wherein the array of relays provides voltage to the fluidic device's electrodes, wherein the mass spectrometer is interfaced to the electrospray ionization source, and wherein the computer controls the array of relays and the mass analyzer and analyzes the mass data generated.
- 58. The system of claim 51 wherein the analyte is selected from the group consisting of proteins and peptides.
- 59. A method for directing a liquid to an analyzer, comprising electroosmotically pumping a liquid from a device having a reservoir containing a liquid, a fluid exit for directing liquid from the device to the analyzer, and a channel for conducting liquid from the reservoir to the fluid exit, wherein the reservoir further comprises an electrode in electrical contact with the liquid in the reservoir.
- 60. The method of claim 59 wherein the device comprises a plurality of reservoirs.
- 61. The method of claim 59 wherein the analyzer is a mass analyzer.
- 62. A method for directing a liquid from a fluidic device to an electrospray ionization source, comprising
providing a fluid path from a fluidic device through a capillary to an electrospray ionization source having an electrospray needle, wherein the device comprises a reservoir containing a liquid, a fluid exit for directing liquid from the device to the capillary, and a channel for conducting liquid from the reservoir to the fluid exit, wherein the reservoir comprises an electrode in electrical contact with the liquid in the reservoir; applying a first voltage to the electrospray needle; and applying a second voltage to the electrode to generate a difference in potential between the electrode and the needle, wherein the difference in potential causes liquid migration from the reservoir to the ionization source.
- 63. A method for directing a liquid from a fluidic device to an electrospray ionization source, comprising
providing a fluid path from a fluidic device through a capillary to an electrospray ionization source having an electrospray needle, wherein the device comprises a plurality of reservoirs each containing a liquid, a fluid exit for directing liquid from the device to the capillary, wherein each reservoir is connected by a channel to a common channel for conducting liquid from each reservoir to the fluid exit, and wherein each reservoir further comprises an electrode in electrical contact with the liquid in the reservoir; applying a first voltage to the electrospray needle; applying a second voltage to a first electrode in a first reservoir to generate a difference in potential between the first electrode and the needle, wherein the difference in potential causes liquid migration from the first reservoir to the ionization source; applying a third voltage to a second electrode in a second reservoir to generate a difference in potential between the second electrode and the needle, wherein the difference in potential causes liquid migration from the second reservoir to the ionization source; and applying a fourth voltage to a third electrode in a third reservoir to generate a difference in potential between the third electrode and the needle, wherein the difference in potential causes liquid migration from the third reservoir to the ionization source.
- 64. The method of claim 63 wherein the voltages to the electrodes are applied sequentially.
- 65. The method of claim 63 wherein the voltage applied to the electrospray needle is in the range from about +1.5 to about +2.0 kV.
- 66. The method of claim 63 wherein the voltage applied to the electrodes is in the range from about −2 to about −8 kV.
- 67. A method for generating a solvent gradient, comprising
providing a fluid path from a fluidic device to a counterelectrode, wherein the device comprises a plurality of reservoirs each containing a liquid, a fluid exit for directing liquid to the counterelectrode, wherein each reservoir is connected by a channel to a common channel for conducting liquid from each reservoir to the fluid exit, and wherein each reservoir further comprises an electrode in electrical contact with the liquid in the reservoir; applying a first voltage to the counterelectrode; applying a second voltage to a first electrode in a first reservoir to generate a difference in potential between the first electrode and the counterelectrode, wherein the difference in potential causes migration of a first liquid from the first reservoir to the common channel; and applying a third voltage to a second electrode in a second reservoir to generate a difference in potential between the second electrode and the counterelectrode, wherein the difference in potential causes migration of a second liquid from the second reservoir to the common channel, wherein the first and second liquids are combined in the common channel to provide a solvent gradient comprising a combination of the first and second liquids.
- 68. The method of claim 67 wherein the counterelectrode comprises an electrospray needle of an electrospray ionization source.
- 69. The method of claim 67 wherein the fluid path from the fluidic device to the counterelectrode further comprises a capillary.
- 70. The method of claim 67 wherein the voltage applied to the electrospray needle is in the range from about +1.5 to about +2.0 kV.
- 71. The method of claim 67 wherein the voltages applied to the electrodes is in the range from about −2 to about −8 kV.
- 72. The method of claim 67 wherein applying voltages to the first and second electrodes comprises,
applying an initial constant voltage to the first electrode and an initial constant slightly lower voltage to the second electrode; ramping the initial voltage applied to the second electrode to about the initial voltage applied to the first electrode and holding the second electrode constant at that voltage; and ramping the initial voltage applied to the first electrode to the about initial voltage applied to the second electrode and holding the first electrode constant at that voltage.
- 73. The method of claim 67 further comprising delivering the solvent gradient from the device.
- 74. The method of claim 73 wherein the solvent gradient is delivered at a flowrate in the range of from about 1 to about 100 nanoliters per minute.
- 75. The method of claim 67 wherein the solvent gradient is delivered to a sample immobilized on a solid phase.
- 76. The method of claim 75 wherein the solid phase is on the fluidic device.
- 77. The method of claim 75 wherein the solid phase is at a position between the fluidic device and the counterelectrode.
- 78. The method of claim 75 wherein the sample comprises an analyte that can be mobilized by the solvent gradient.
- 79. The method of claim 78 further comprising directing the mobilized analyte to an electrospray ionization source, ionizing the analyte to provide an ionized analyte, introducing the ionized analyte into a mass analyzer, and identifying the analyte.
- 80. The method of claim 79 wherein the analyte is selected from the group consisting of a protein and a peptide.
- 81. The method of claim 79 wherein the mass analyzer is a tandem mass spectrometer.
- 82. A method for identifying an analyte by mass analysis, comprising
directing a liquid containing the analyte to an electrospray ionization source, wherein the liquid is electroosmotically pumped from a device having a reservoir for containing the liquid, a fluid exit for directing the liquid from the device to the analyzer, and a channel for conducting the liquid from the reservoir to the fluid exit, wherein the reservoir further comprises an electrode in electrical contact with the liquid in the reservoir, ionizing the analyte at the electrospray ionization source to provide an ionized analyte; directing the ionized analyte into a mass analyzer interfaced with the ionization source; obtaining mass data for the ionized analyte; and identifying the analyte based on the mass data obtained.
- 83. The method of claim 82 wherein the device comprises a plurality of reservoirs.
- 84. The method of claim 82 wherein the directing a liquid from the device to the electrospray source further includes directing the liquid through a capillary.
- 85. The method of claim 82 wherein the mass analyzer is a tandem mass spectrometer.
- 86. The method of claim 82 wherein identifying the analyte comprises searching sequence databases with mass data selected from the group consisting of peptide masses generated by chemical or enzymatic protein fragmentation and CID spectra of selected peptides.
- 87. The method of claim 82 wherein the analyte is selected from the group consisting of a protein and a peptide.
- 88. The method of claim 82 wherein the liquid is a digest of a protein comprising peptides.
- 89. The method of claim 88 wherein the protein is identified by searching sequence data bases with peptides masses obtained from the mass analysis of the digest's peptides.
- 90. The method of claim 88 wherein the protein is identified by searching sequence data bases with CID spectra of selected peptides.
Government Interests
[0001] This invention was made in part with government support under grant T32HG00035-3 awarded by the National Institutes' of Health and grant BIR9214821AM04 awarded by the National Science Foundation. The government has certain rights in the invention.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60069398 |
Dec 1997 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
09209880 |
Dec 1998 |
US |
Child |
10053485 |
Jan 2002 |
US |