Formulation of acoustically activatable particles having low vaporization energy and methods for using same
An acoustically activatable particle of material includes a first substance that includes a component that is a gas 25° C. and atmospheric pressure. A second substance, different from the first substance, encapsulates the first substance to create a droplet or emulsion that is stable at room temperature and atmospheric pressure. At least some of the first substance exists in a gaseous phase at the time of encapsulation of the first substance within the second substance to form a bubble. After formation of the bubble, the bubble is condensed into a liquid phase, which causes the bubble to transform into the droplet or emulsion having a core consisting of a liquid. The droplet or emulsion is an activatable phase change agent having a core consisting of a liquid at 25° C. and atmospheric pressure. The first substance has a boiling point below 25° C. at atmospheric pressure.
1. A method of producing particles of materials for ultrasound activation, comprising:
condensing, from a gaseous phase to a liquid phase, a first substance comprising at least one component that is a perfluorocarbon or perfluorochemical having a boiling point below 25° C. at atmospheric pressure;
extruding or emulsifying the first substance into or in the presence of a second substance to create a droplet having a diameter of less than one micron and in which the first substance is encapsulated by the second substance and wherein at least some of the first substance exists in the liquid phase at the time of encapsulation of the first substance within the second substance, and wherein the droplet is an activatable phase change agent that remains a droplet having a core that will remain in the liquid phase at a boiling point of the first substance and atmospheric pressure.
2. The method of claim 1 wherein the first substance comprises at least one of decafluorobutane (DFB) or octafluoropropane (OFP).
3. The method of claim 1 wherein causing the first substance to condense to a liquid phase comprises cooling the first substance.
4. The method of claim 3 wherein causing the first substance to condense to a liquid phase comprises cooling the first substance to a temperature that is below the liquid-to-gas phase transition temperature of a component of the first substance having the lowest liquid-to-gas phase transition temperature.
5. The method of claim 1 wherein causing the first substance to condense to a liquid phase comprises compressing the first substance.
6. The method of claim 5 wherein causing the first substance to condense to a liquid phase comprises compressing the first substance to a pressure that is above the gas-to-liquid phase transition pressure of a component of the first substance having the highest gas-to-liquid phase transition pressure.
7. The method of claim 1 wherein the second substance comprises at least one of a lipid, a protein, a polymer, a gel, a surfactant, a peptide, or a sugar.
8. The method of claim 1 wherein the second substance comprises lung surfactants, amphiphiles, proteins, or peptide components thereof in a sufficient quantity to fully encapsulate the liquid phase of the first substance.
9. The method of claim 1 wherein the amphiphiles comprise at least one of amphiphilic polymers and copolymers, amphiphilic peptides, amphiphilic dendrimers, or amphiphilic nucleic acids.
10. The method of claim 1 wherein the first substance consists of a single perfluorocarbon or perfluorochemical having a single activation energy.
11. The method of claim 1 wherein extruding or emulsifying the first substance into or in the presence of a second substance includes extruding the first substance through a filter.
12. The method of claim 11 wherein the filter has a pore size greater than a desired particle size.
13. The method of claim 1 wherein extruding or emulsifying the first substance into or in the presence of a second substance includes using a microfluidics technique to produce the droplet in which the first substance is encapsulated within the second substance.
14. The method of claim 13 wherein using the microfluidics technique includes using a flow focusing or T junction in a microfluidics device to produce the droplet in which the first substance is encapsulated within the second substance.