Acoustic ejection into small openings
View Patent ↗Provided is a method of transporting fluid which involves acoustic ejection into a small opening. The opening may be, for example, the inlet opening of a sample vessel. Alternatively, it may be an opening in a microfluidic device. The ejection is typically, but not necessarily carried out through the application of focused acoustic energy. The fluid being transported typically comprises a moiety of interest for analysis or further processing, which may be a biomolecule. The volumes of transported fluid may be in the nanoliter or picoliter range. Ejection may occur from very small volumes and the ejected droplet may carry away a significant fraction of the volume from which ejection occurs.
1. A device for transport of a fluid sample, comprising:
(a) a reservoir holding a fluid sample, the fluid sample having a surface that allows a droplet to ejected therefrom;
(b) an ejector comprising an acoustic radiation generator for generating acoustic radiation and a focusing means for focusing the acoustic radiation at a focal point near the surface of the fluid sample; and
(c) a means for positioning the ejector in controlled and repeatable acoustic coupling relationship to the reservoir to eject a droplet of the fluid sample from the reservoir into an opening having a limiting dimension of no more than about 300 μm, and
(d) an acoustic system for determining the orientation of the fluid surface.
2. The device of claim 1 , where the opening is an inlet opening of a sample vessel.
3. The device of claim 2 , wherein the sample vessel is an ionization chamber which forms part of a mass spectrometer.
4. The device of claim 3 , wherein the mass spectrometer is a time-of-flight mass spectrometer.
5. The device of claim 1 , wherein the fluid sample occupies a volume of no more than about 100 μL.
6. The device of claim 5 , wherein the fluid sample occupies a volume of no more than about 10 μL.
7. The device of claim 6 , wherein the fluid sample occupies a volume of no more than about 1 μL.
8. The device of claim 7 , wherein the fluid sample occupies a volume of about 10 pL to about 100 nL.
9. The device of claim 1 , wherein the ejector is configured to eject a droplet having a volume of no more than about 1 nL.
10. The device of claim 9 , wherein the ejector is configured to eject a droplet having a volume of no more than about 1 pL.
11. The device of claim 10 , wherein the ejector is configured to eject a droplet having a volume of no more than about 100 fL.
12. The device of claim 1 , wherein the ejector is configured to eject no more than about 5 percent of the fluid sample per droplet.
13. The device of claim 1 , wherein the fluid sample comprises a moiety of interest having a molecular weight of about 100 daltons to about 100 kilodaltons.
14. The device of claim 13 , wherein the molecular weight is about 1 to about 100 kilodaltons.
15. The device of claim 1 , wherein the fluid sample further comprises water.
16. The device of claim 1 , wherein the fluid sample comprises a moiety of interest which is nonmetallic.
17. The device of claim 16 , wherein the moiety of interest is an organic compound.
18. The device of claim 17 , wherein the organic compound is a biomolecule.
19. The device of claim 18 , wherein the biomolecule is nucleotidic.
20. The device of claim 18 , wherein the biomolecule is peptidic.
21. The device of claim 1 , further comprising a detector for detecting reflected acoustic radiation from the fluid sample.
22. The device of claim 2 , further comprising a charging means for electrically charging the fluid sample.
23. The device of claim 22 , wherein the charging means is configured to electrically charge the surface of the fluid sample.
24. The device of claim 1 , wherein the sample vessel comprises a microfluidic device.
25. The device of claim 1 , wherein the sample vessel forms part of a microfluidic device.
26. The device of claim 1 , wherein the reservoir forms part of a microfluidic device.
27. The device of claim 1 , comprising a plurality of reservoirs, wherein each reservoir holds a fluid sample comprising a sample moiety, and the means for positioning the ejector is adapted to position the ejector in acoustic coupling relationship to each of the reservoirs to eject a droplet of fluid sample into the sample vessel.
28. The device of claim 27 , wherein the reservoirs are arranged in an array.
29. The device of claim 27 , wherein the reservoirs are provided as integrated members of a single substrate.
30. The device of claim 29 , wherein the substrate surface is substantially flat.
31. The device of claim 27 , further comprising a means for altering the spatial relationship of at least one reservoir with respect to the sample vessel.
32. The device of claim 1 , further comprising a coupling fluid interposed between the ejector and the reservoir for acoustic coupling.
33. The device of claim 1 , wherein the limiting dimension does not exceed about 100 μm.
34. The device of claim 33 , wherein the limiting dimension does not exceed about 50 μm.
35. The device of claim 34 , wherein the limiting dimension does not exceed about 20 μm.
36. The device of claim 1 , wherein the reservoir interior volume is no more than about 1 μL.
37. The device of claim 36 , wherein the reservoir interior volume is no more than about 100 nL.
38. The device of claim 37 , wherein the reservoir interior volume is no more than about 50 nL.
39. The device of claim 2 , wherein the sample vessel has an interior volume of no more than about 5 μL.
40. The device of claim 39 , wherein the sample vessel interior volume is not more than about 1 μL.
41. The device of claim 40 , wherein the sample vessel interior volume is no more than about of about 100 nL.
42. The device of claim 41 , wherein the sample vessel interior volume is no more than about 50 nL.
43. The device of claim 2 , wherein the ejector is configured to eject at least about 50% of the fluid sample through the inlet opening into the sample vessel.
44. The device of claim 43 , wherein the ejector is configured to eject at least about 75% of the fluid sample through the inlet opening into the sample vessel.
45. The device of claim 44 , wherein the ejector is configured to eject at least about 85% of the fluid sample through the inlet opening into the sample vessel.
46. The device of claim 2 , wherein the sample vessel comprises a substantially flat surface and the inlet opening is located on the flat surface.
47. The device of claim 2 , wherein the sample vessel comprises a capillary and the inlet opening provides access to an interior region of the capillary.
48. The device of claim 47 , wherein the inlet opening is located at a terminus of the capillary.
49. The device of claim 48 , wherein the interior region of the capillary is axially symmetric.
50. The device of claim 49 , wherein at least a portion of the vessel is electrically conductive.
51. The device of claim 50 , wherein at least a portion of the vessel is electrically insulating.
52. The device of claim 1 , wherein the sample vessel comprises a microfluidic device.
53. A method for introducing a sample molecule into a sample vessel of a device which comprises an opening of limiting dimension no more than about 300 μm for processing and/or analyzing a sample moiety, comprising:
(a) providing a reservoir holding a fluid sample comprising the sample moiety;
(b) determining by acoustic means the orientation of a surface of the fluid sample; and
(c) directing focused acoustic radiation at a point near the surface of the fluid sample to eject a droplet of the fluid sample from the surface of the fluid sample along a predetermined trajectory into the opening of limiting dimension no more than about 300 μm.
54. The method of claim 53 , wherein the sample vessel is an ionization chamber.
55. The method of claim 54 , wherein the device is a mass spectrometer.
56. The method of claim 55 , wherein the mass spectrometer is a time-of-flight mass spectrometer.
57. The method of claim 53 , further comprising repeating step (c).
58. The method of claim 57 , wherein the ejected droplets are substantially identical in size.
59. The method of claim 57 , wherein no more than about 5 percent of the sample fluid is ejected per droplet.
60. The method of claim 57 , wherein the predetermined trajectories of the ejected droplets are substantially identical.
61. The method of claim 55 , wherein the predetermined trajectory passes through a region where there exists a nonnegligible electric field.
62. The method of claim 53 , wherein the sample moiety has a molecular weight of about 100 daltons to about 100 kilodaltons.
63. The method of claim 62 , wherein the molecular weight is about 1 to about 100 kilodaltons.
64. The method of claim 54 , wherein the sample moiety has a molecular weight to charge ratio of about 100 daltons/charge to about 100 kilodaltons/charge.
65. The method of claim 53 , wherein the fluid sample further comprises water.
66. The method of claim 53 , wherein the sample moiety is nonmetallic.
67. The method of claim 66 , wherein the sample moiety an organic compound.
68. The method of claim 67 , wherein the organic compound is a biomolecule.
69. The method of claim 68 , wherein the biomolecule is nucleotidic.
70. The method of claim 68 , wherein the biomolecule is peptidic.
71. The method of claim 53 , further comprising, after step (a) and before step (c), (a′) transmitting acoustic radiation through the fluid sample and detecting reflected acoustic radiation.
72. The method of claim 54 , further comprising, after step (a) and before step (c), (a′) electrically charging the fluid sample.
73. The method of claim 72 , wherein step (a′) is carried out by charging the surface of the fluid sample.
74. The method of claim 72 , wherein step (a′) is carried out by charging the reservoir.
75. The method of claim 53 , wherein the sample vessel comprises a microfluidic device.
76. The method of claim 53 , wherein the sample vessel represents a portion of a microfluidic device.
77. The method of claim 53 , wherein the reservoir represents a portion of a microfluidic device.
78. A method for the transport of a droplet of a fluid sample into a sample vessel, comprising:
(a) providing a reservoir holding a fluid sample having a volume of no more than about 5 μL;
(b) determining by acoustic means the orientation of a surface of the fluid sample; and
(c) ejecting at least 25% of the fluid sample through an inlet opening of the sample vessel, wherein the inlet opening has a limiting dimension of no more than about 300 μm.
79. The method of claim 78 , wherein step (c) is carried out by directing focused acoustic radiation at a point near the sample fluid surface to eject a droplet of the fluid sample from the surface of the fluid sample through the inlet opening.
80. The method of claim 79 , wherein step (c) is repeated.
81. The method of claim 78 , wherein the droplet comprises a sample molecule that exits the sample vessel through an outlet opening.
82. The method of claim 78 , wherein the droplet is electrically charged.
83. The method of claim 78 , wherein the sample vessel comprises a microfluidic device.
84. The method of claim 78 , wherein the sample vessel represents a portion of a microfluidic device.