CA2577457C - Microbubble medical devices - Google Patents
Microbubble medical devices Download PDFInfo
- Publication number
- CA2577457C CA2577457C CA 2577457 CA2577457A CA2577457C CA 2577457 C CA2577457 C CA 2577457C CA 2577457 CA2577457 CA 2577457 CA 2577457 A CA2577457 A CA 2577457A CA 2577457 C CA2577457 C CA 2577457C
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- fluid
- bubble
- bubbles
- flow path
- container
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Abstract
Method and medical devices for generating and stabilizing micro- or nano-bubbles, and systems and methods for therapeutic applications using the bubbles, is provided. Two novel bubble generating means are provided: in-line capillary tubes and mix chambers flow focusing, and cross flow bubble generation with optimized bubble detachment means. The micro-bubbles may be used to enhance therapeutic benefits such as ultrasound-guided precision drug delivery and real--time verification, acoustic activation of large tumour masses, enhanced acoustic activation through longer retention of therapeutic agents at the point of interest, enhancement of high intensity focused ultrasound treatments, light activation of photodynamic drugs at a depth within a patient using extracorporeal light sources, probes, or sonoluminescence, and initiation of time reversal acoustics focused ultrasound to permit highly localized treatment.
Claims (32)
1. A device for generating bubbles for introduction into a body comprising:
a fluid container for a fluid;
a flow path communicating with the fluid container for infusing a second fluid flow with said fluid container, said flow path being defined at least in part by the fluid container;
a fluid discharge means for applying a pressure to the fluids causing the fluids to travel the flow path; and a bubble generating means communicating with the flow path for generating bubbles, wherein the bubble generating means comprising:
a fluid displacement means for infusing air, compressed gas, or other fluids into the fluid container; and a second fluid displacement means for driving the fluids through a fluid conduit system comprising one or more of a capillary tube and one or more of a mix chamber.
a fluid container for a fluid;
a flow path communicating with the fluid container for infusing a second fluid flow with said fluid container, said flow path being defined at least in part by the fluid container;
a fluid discharge means for applying a pressure to the fluids causing the fluids to travel the flow path; and a bubble generating means communicating with the flow path for generating bubbles, wherein the bubble generating means comprising:
a fluid displacement means for infusing air, compressed gas, or other fluids into the fluid container; and a second fluid displacement means for driving the fluids through a fluid conduit system comprising one or more of a capillary tube and one or more of a mix chamber.
2. A device according to claim 1 further comprising a fluid vessel storage means communicating with the flow path for storage of the generated bubbles for transfer to and infusion within a body at a point of interest.
3. A device according to claim 1 further comprising an injection means communicating with the flow path for directing and conveying the fluid travelling the flow path within a body at a point of interest.
4. A device according to claim 1 further comprising:
a second container for an additional fluid;
a second flow path communicating with the second container for directing fluid flow from the second container, said second flow path being defined at least in part by the second container; and operator control means for selecting fluids and relative concentrations of the fluid and the additional fluid for intermixing;
wherein the first flow path and the second flow path are joined for intermixing.
a second container for an additional fluid;
a second flow path communicating with the second container for directing fluid flow from the second container, said second flow path being defined at least in part by the second container; and operator control means for selecting fluids and relative concentrations of the fluid and the additional fluid for intermixing;
wherein the first flow path and the second flow path are joined for intermixing.
5. A device for generating bubbles comprising:
a plurality of fluid containers, each of the plurality of fluid containers having a fluid discharge means disposed for applying a pressure on a fluid in the container;
a plurality of fluid conduits, each connected to each of the plurality of fluid containers at a first end and each connected to a body conduit at a second end;
an injection means connected to the body conduit for discharging the fluid from a distal end, the injection means adapted to convey the fluid into a body at a point of interest; and a bubble generating means disposed in at least one of the plurality of fluid conduits;
wherein for each of the plurality of fluid containers, a flow path is defined from the container through the fluid conduit, the body conduit and the injection means for discharge from the distal end; wherein for each of the plurality of fluid containers a high or low pressure from the fluid discharge means causes the fluid to travel the flow path; and wherein a first fluid in the one of the plurality of fluid conduits travels the flow path through bubble generating means for generating bubbles comprised of the first fluid, and wherein the bubble generating means comprising:
a fluid displacement means for infusing air, compressed gas, or other fluids into the fluid container; and a second fluid displacement means for driving the fluids through a fluid conduit system comprising one or more of a capillary tube and one or more of a mix chamber.
a plurality of fluid containers, each of the plurality of fluid containers having a fluid discharge means disposed for applying a pressure on a fluid in the container;
a plurality of fluid conduits, each connected to each of the plurality of fluid containers at a first end and each connected to a body conduit at a second end;
an injection means connected to the body conduit for discharging the fluid from a distal end, the injection means adapted to convey the fluid into a body at a point of interest; and a bubble generating means disposed in at least one of the plurality of fluid conduits;
wherein for each of the plurality of fluid containers, a flow path is defined from the container through the fluid conduit, the body conduit and the injection means for discharge from the distal end; wherein for each of the plurality of fluid containers a high or low pressure from the fluid discharge means causes the fluid to travel the flow path; and wherein a first fluid in the one of the plurality of fluid conduits travels the flow path through bubble generating means for generating bubbles comprised of the first fluid, and wherein the bubble generating means comprising:
a fluid displacement means for infusing air, compressed gas, or other fluids into the fluid container; and a second fluid displacement means for driving the fluids through a fluid conduit system comprising one or more of a capillary tube and one or more of a mix chamber.
6. The device according to any one of claims 1-5, wherein the fluid comprise one member selected from a group consisting of: a therapeutic agent, a carrier, an additive, a stabilizer, a bioadhesive, or a surfactant, and a combination thereof.
7. The device according to claim 6, wherein the therapeutic agent is selected from a group consisting of: a liquid organic drug; a liquid inorganic drug; a solid drug suspended in a fluid; an acoustically activated drug delivery system, suspended in a fluid; a therapeutic chemical including ethanol; a therapeutic chemical including acid; an embolization fluid; an embolization gel; embolization gel suspension;
a photodynamic drug; a radioisotope labelled drug; a radioisotope labelled particle;
an imaging system contrast agent for imaging systems including CT scans, MRI, ultrasound, or X-ray, and a combination thereof.
a photodynamic drug; a radioisotope labelled drug; a radioisotope labelled particle;
an imaging system contrast agent for imaging systems including CT scans, MRI, ultrasound, or X-ray, and a combination thereof.
8. The device according to any one of claims 1-7, wherein all or part of the flow path is defined in a needle, a catheter, a stylet, a guide wire, a laparoscope, an endoscope, a multiple lumen needle, or a multiple lumen catheter.
9. The device according to any one of claims 1-8, wherein the bubble generating means comprises an in-line flow focusing system comprising:
a means for verifying the generated bubbles size and concentration through impedance measuring.
a means for verifying the generated bubbles size and concentration through impedance measuring.
10. The device according to any one of claims 1-9, wherein the bubble generating means comprises an in-line flow focusing system comprising:
a means for infusing additional fluids or additives into the fluid conduit system on demand.
a means for infusing additional fluids or additives into the fluid conduit system on demand.
11. The device according to any one of claims 1-10, wherein the bubble generating means comprises a cross flow bubble detachment system comprising:
means for displacing a carrier fluid in order to induce recirculating or in-line flow in a carrier fluid.
means for displacing a carrier fluid in order to induce recirculating or in-line flow in a carrier fluid.
12. The device according to claim 11, wherein the bubble generating means comprises a cross flow bubble detachment system comprising:
means for displacing a bubble fluid into the carrier fluid for repeated bubble formation and detachment.
means for displacing a bubble fluid into the carrier fluid for repeated bubble formation and detachment.
13. The device according to claim 12, further comprising means for promoting bubble detachment comprising:
hydrofoils or funnels for directing the carrier fluid flow to promote bubble detachment;
alignment of the fluid conduit in-line with carrier fluid flow;
vibration means for vibrating the fluid conduit at a location of bubble detachment or the fluid proximate to the point of bubble.
hydrofoils or funnels for directing the carrier fluid flow to promote bubble detachment;
alignment of the fluid conduit in-line with carrier fluid flow;
vibration means for vibrating the fluid conduit at a location of bubble detachment or the fluid proximate to the point of bubble.
14. The device according to claim 13, wherein the vibration means is a piezo source, and wherein the piezo source is adjustable in real time.
15. The device according to claim 14, further comprising means for displacing the carrier fluid selected from a group consisting of: a pump; fluid pressure;
vacuum source; a rotating drum; propeller; and a suitable moving means for inducing in-line or recirculating fluid flow.
vacuum source; a rotating drum; propeller; and a suitable moving means for inducing in-line or recirculating fluid flow.
16. The device according to any one of claims 1-15, further comprising means for stabilizing shrinking, transient bubbles at a desired bubble size.
17. The device according to any one of claims 1-16, further comprising means for directing the bubbles and carrier fluid to a stabilizing chamber.
18. The device according to any one of claims 1-17, further comprising means for stabilizing shrinking, transient bubbles at a desired bubble size comprising:
means for transmitting an ultrasonic pulse at the bubbles for a sufficient time period for the bubbles to shrink and to stabilize at a size corresponding to the resonant frequency of the ultrasonic pulse.
means for transmitting an ultrasonic pulse at the bubbles for a sufficient time period for the bubbles to shrink and to stabilize at a size corresponding to the resonant frequency of the ultrasonic pulse.
19. The device according to claim 18, wherein the means for stabilizing shrinking, transient bubbles at a desired bubble size further comprises means for adjusting the frequency, intensity, duration, and mode of the ultrasonic pulse in real time.
20. The device according to any one of claims 1-19, wherein at least a part of the device is adapted to be hand held for directing fluid traveling the flow path to the body at the point of interest.
21. The device according to any one of claims 1-20, further comprising temperature control means for modulating a temperature of the fluid.
22. The device according to claim 21, wherein the temperature control means includes one or more of a refrigeration source, a heating source, a temperature sensor, a temperature control, or a thermal insulating material.
23. The device according to any one of claims 1-22, wherein a flow rate of the fluid is adjustable in real-time.
24. The device according to claim 1, wherein the fluid container is a syringe and the fluid discharge means is a plunger slidably disposed within the syringe.
25. The device of according to any one of claim 1-24, further comprising a storage vessel positioned downstream of the bubble generating means for receiving the fluid; wherein the pressure causes the fluid to travel the flow path into the storage vessel.
26. A system for acoustically activating the bubbles comprising:
a device according to any one of claims 1 to 25; and acoustic activation means for generating acoustic pulses;
wherein the acoustic activation means is selected from the group consisting of an extracorporeal ultrasound transducer, and a transducer array; and wherein the acoustic activation of the bubbles induces one member selected from the group consisting of: inertial cavitations; non-inertial cavitations;
bubble resonance; bubble destruction; and a combination thereof.
a device according to any one of claims 1 to 25; and acoustic activation means for generating acoustic pulses;
wherein the acoustic activation means is selected from the group consisting of an extracorporeal ultrasound transducer, and a transducer array; and wherein the acoustic activation of the bubbles induces one member selected from the group consisting of: inertial cavitations; non-inertial cavitations;
bubble resonance; bubble destruction; and a combination thereof.
27. A system for enhancing high intensity focused ultrasound (HIFU) treatment comprising:
a device according to any one of claims 1 to 25; and high intensity focused acoustic pulses;
wherein the high intensity focused ultrasound means is selected from the group consisting of a HIFU probe for minimally invasive tumour ablation, an extracorporeal, high intensity ultrasound transducer, and a transducer array for transmitting pulses; and wherein the HIFU energy applied to the bubbles may induce one member selected from the group consisting of. inertial cavitations; non-inertial cavitations; bubble resonance; bubble destruction; and a combination thereof.
a device according to any one of claims 1 to 25; and high intensity focused acoustic pulses;
wherein the high intensity focused ultrasound means is selected from the group consisting of a HIFU probe for minimally invasive tumour ablation, an extracorporeal, high intensity ultrasound transducer, and a transducer array for transmitting pulses; and wherein the HIFU energy applied to the bubbles may induce one member selected from the group consisting of. inertial cavitations; non-inertial cavitations; bubble resonance; bubble destruction; and a combination thereof.
28. The system according to any one of claims 26-27, further comprising means for focusing the pulses such as a time reversal acoustics array.
29. A use of the device according to any one of claims 1 to 25.
30. A use of the device according to any one of claims 1 to 25 for enhancing high intensity focused ultrasound (HIFU) treatment.
31. A use of the device according to any one of claims 1 to 25 for treatment of cancers and tumours, including retinoblastoma, esophageal and liver cancers, vascular disease, or neurological disease.
32. A use of the device according to any one of claims 1 to 25 for inducing cell necrosis in diseased tissue.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58899506A | 2006-10-27 | 2006-10-27 | |
| US11/588,995 | 2006-10-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2577457A1 CA2577457A1 (en) | 2008-04-27 |
| CA2577457C true CA2577457C (en) | 2011-04-19 |
Family
ID=39367059
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2577457 Expired - Fee Related CA2577457C (en) | 2006-10-27 | 2007-02-06 | Microbubble medical devices |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2577457C (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8257338B2 (en) * | 2006-10-27 | 2012-09-04 | Artenga, Inc. | Medical microbubble generation |
| US8905992B2 (en) | 2011-11-07 | 2014-12-09 | General Electric Company | Portable microbubble and drug mixing device |
| CN107390100B (en) * | 2017-08-03 | 2019-07-19 | 四川大学 | A kind of power cable partial discharge positioning method based on time reversal |
| CN111319056B (en) * | 2020-03-02 | 2021-04-06 | 河北工业大学 | Micro-nano particle nondestructive carrying method and device based on controllable micro-scale bubbles |
-
2007
- 2007-02-06 CA CA 2577457 patent/CA2577457C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2577457A1 (en) | 2008-04-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20150206 |