Precipitation of solid particles from droplets formed using focused acoustic energy

1. A method for generating solid particles of substantially identical size, the method comprising:

(a) applying focused acoustic radiation to a solution in a reservoir in a manner effective to eject a droplet of the solution from the reservoir, wherein the solution is comprised of a compound of interest dissolved in a solvent;

(b) subjecting the droplet to a condition that allows the compound to precipitate out of solution, thereby forming a solid particle;

(c) repeating steps (a) and (b) so as to form solid particles of substantially identical size.

2. The method of claim 1 , wherein step (a) comprises applying focused acoustic radiation to the solution in the reservoir at a plurality of loci so as to eject droplets therefrom.

3. The method of claim 2 , wherein droplets are ejected from the loci substantially simultaneously.

4. The method of claim 2 , wherein droplets are ejected at different times.

5. The method of claim 1 , wherein step (b) comprises exposing the droplet to an antisolvent.

6. The method of claim 5 , wherein the antisolvent is a supercritical fluid.

7. The method of claim 5 , wherein the antisolvent is gaseous.

8. The method of claim 1 , wherein step (b) comprises heating the droplet.

9. The method of claim 1 , wherein step (b) comprises cooling the droplet.

10. The method of claim 1 , wherein step (b) comprises exposing the droplet to a reduced pressure.

11. The method of claim 1 , wherein step (b) comprises crystallizing the compound.

12. The method of claim 1 , wherein step (b) comprises allowing the compound to chemically react with another compound in the droplet.

13. The method of claim 1 , wherein step (b) comprises allowing the compound to polymerize.

14. The method of claim 1 , wherein the particles generated are substantially free of solvent.

15. The method of claim 1 , wherein the generated particles contain a fluid.

16. The method of claim 1 , wherein the reservoir contains no more than about 100 nanoliters of the solution.

17. The method of claim 16 , wherein the reservoir contains no more than about 10 nano liters of the solution.

18. The method of claim 1 , wherein the applied focused acoustic radiation has a characteristic wavelength and travels a distance of no more than 50 times the characteristic wavelength through the solution before a droplet is ejected from the reservoir.

19. The method of claim 18 , wherein the distance traveled by the acoustic radiation is no more than 10 times the characteristic wavelength of the acoustic radiation.

20. The method of claim 1 , wherein the solution is substantially saturated with the compound of interest.

21. The method of claim 1 , wherein the solvent is aqueous.

22. The method of claim 1 , wherein the solvent is nonaqueous.

23. The method of claim 22 , wherein the solvent is organic.

24. The method of claim 1 , wherein the solvent is polar.

25. The method of claim 1 , wherein the solvent is nonpolar.

26. The method of claim 1 , wherein the compound is a biomolecule.

27. The method of claim 1 , wherein the compound is a pharmaceutical agent.

28. The method of claim 27 , wherein the pharmaceutical agent is hydrophilic.

29. The method of claim 27 , wherein the pharmaceutical agent is lipophilic.

30. The method of claim 27 , wherein the pharmaceutical agent is peptidic.

31. The method of claim 27 , wherein the pharmaceutical agent is a respiratory drug.

32. The method of claim 31 , wherein the respiratory drug is selected from the group consisting of anti-inflammatory corticosteroids, bronchodilators, and mixtures thereof.

33. The method of claim 27 , wherein the pharmaceutical agent is a diagnostic agent.

34. The method of claim 27 , wherein the pharmaceutical agent is solublized and/or stabilized by a membrane lipid.

35. The method of claim 34 , wherein the membrane lipid is selected from the group consisting of sphingomyelin, phosphatidylethanolamine, phosphatidyicholine, and combinations thereof.

36. The method of claim 1 , wherein the focused acoustic radiation is applied using a focusing means having an F-number of less than 2.

37. The method of claim 36 , wherein the focused acoustic radiation is applied using a focusing means having an F-number less than 1.

38. A method for generating a solid particle coated with a compound of interest, the method comprising:

(a) providing a reservoir containing a discrete localized volume and a solution comprised of the compound of interest dissolved in a solvent, wherein the discrete localized volume has a composition different from that of the solution;

(b) applying focused acoustic radiation to the solution in a manner effective to eject a droplet from the reservoir, wherein the droplet contains the discrete localized volume and the solution;

(c) subjecting the droplet to a condition that allows the compound of interest to precipitate out of solution onto the localized volume, thereby forming a solid particle coated with the compound of interest.

39. The method of claim 38 , wherein the discrete localized volume contains a pharmaceutical agent.

40. The method of claim 39 , wherein the pharmaceutical agent is a pharmacologically active compound.

41. The method of claim 39 , wherein the pharmaceutical agent is an excipient.

42. The method of claim 38 , wherein the discrete localized volume is a solid.

43. The method of claim 38 , wherein the size of the solid particle formed is in the range of about 0.1 nm to about 10 μm.

44. The method of claim 43 , wherein the size of the solid particle formed is in the range of about 2 μm to about 7 μm.

45. The method of claim 38 , wherein the compound of interest forms a coating having a thickness of no more than about 1 μm.

46. The method of claim 45 , wherein the compound of interest forms a coating having a thickness of no more than about 100 nm.

47. The method of claim 46 , wherein the compound of interest forms a coating having a thickness of about 10 nm to about 100 nm.

48. The method of claim 38 , wherein the compound of interest forms a coating having a thickness no more than about 10% of the size of the particle.

49. The method of claim 38 , wherein the compound of interest forms no subparticle larger than 10% of the size of the particle.

50. A method for generating a solid particle comprised of different compounds of interest, the method comprising:

(a) providing a reservoir containing immiscible fluids, wherein each fluid in the reservoir contains a different compound of interest, and at least one fluid is comprised of a solution of a compound of interest dissolved in a solvent;

(b) applying focused acoustic radiation to at least one fluid contained in the reservoir in a manner effective to eject a droplet from the reservoir, wherein the droplet is comprised of at least two of the immiscible fluids;

(c) subjecting the droplet to a condition that allows the dissolved compound to precipitate out of solution, thereby generating the solid particle.

51. The method of claim 50 , wherein the each fluid is comprised of a solution of a different compound of interest as a solute in a solvent.

52. The method of claim 50 , wherein the compound of interest contained in at least one fluid is not a solute in a solvent.

53. The method of claim 50 , wherein at least one fluid is solvent free.

54. The method of claim 52 , wherein at least one of the compounds of interest is a pharmaceutical agent.

55. The method of claim 54 , wherein at least two of the compounds of interest are pharmaceutical agents.

56. The method of claim 55 , wherein at least one pharmaceutical agent is a pharmacologically active compound and another pharmaceutical agent is an excipient.

57. The method of claim 50 , wherein the immiscible fluids contained in the reservoir are comprised of a lower fluid layer and an upper fluid layer.

58. The method of claim 57 , wherein the lower fluid layer is comprised of a solution of a compound of interest as a solute in a solvent.

59. The method of claim 57 , wherein the upper fluid layer is comprised of a solution of a compound of interest as a solute in a solvent.

60. The method of claim 50 , wherein one of the fluids is aqueous and another of the fluids is nonaqueous.

61. The method of claim 60 , wherein the nonaqueous fluid is comprised of a lipidic material.

62. The method of claim 50 , wherein the at least one solute compound is biomolecule.

63. The method of claim 50 , wherein the at least one solute compound is a pharmaceutical agent.

64. The method of claim 50 , wherein the solid particle generated is comprised of an outer region encapsulating a core region.

65. The method of claim 64 , wherein the outer region is comprised of the at least one solute compound.

66. The method of claim 64 , wherein the core region is comprised of the at least one solute compound.

67. The method of claim 64 , wherein the outer region occupies no more than about 50% of the total particle volume.

68. The method of claim 67 , wherein the outer region occupies no more than about 10% of the total particle volume.

69. The method of claim 68 , wherein the outer region occupies no more than about 5% of the total particle volume.

70. The method of claim 50 , further comprising, after step (a) and before step (b), acoustically assessing the composition, volume and/or depths of the fluids in the reservoir.

71. A method for generating at least one solid particle, each containing a compound of interest, the method comprising:

(a) applying focused acoustic radiation to a solution in a reservoir in a manner effective to eject a droplet of the solution from the reservoir, wherein the solution is comprised of a compound of interest dissolved in a solvent; and

(b) subjecting the droplet to a condition that allows the compound to precipitate from the solution at a plurality of loci, thereby generating at least one solid particle.

72. The method of claim 71 , wherein a single solid particle is formed from the droplet.

73. The method of claim 72 , wherein the single solid particle is comprised of a plurality of distinct regions, and each region is formed from the precipitation of the compound from solution.

74. The method of claim 73 , wherein the distinct regions are substantially identical in size.

75. The method of claim 71 , wherein a plurality of solid particles is generated from the droplet.

76. The method of claim 75 , wherein the solid particles are substantially identical in size.

77. The method of claim 71 , wherein the size of the at least one particle is in the range of about 0.1 nm to about 1 μm.

78. The method of claim 77 , wherein the size of the at least one particle is in the range of about 10 nm to about 100 nm.

79. The method of claim 71 , wherein the reservoir further contains a discrete localized volume having a composition different from the composition of the solution, and the ejected droplet contains the discrete localized volume.

80. The method of claim 79 , wherein the compound of interest is deposited onto a surface of the localized volume.

81. The method of claim 71 , wherein the reservoir further contains a fluid that is immiscible with the solution.

82. A system for generating solid particles of a plurality of compounds of interest, comprising:

a reservoir containing a solution of a first compound of interest as a solute in a solvent and a second compound of interest, wherein the second compound of interest is contained in a fluid that is immiscible with the solution and/or in a discrete localized volume within the solution;

an acoustic ejector comprising an acoustic radiation generator for generating acoustic radiation and a focusing means for focusing the acoustic radiation at a focal point within the solution in the reservoir so as to eject a droplet therefrom; and

a means for positioning the ejector in acoustic coupling relationship to the reservoir.

83. The system of claim 82 , further comprising a means for subjecting the droplet to a condition that allows the first compound of interest to precipitate out of solution.