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Bubble jetting member and method for producing same, gas/liquid jetting member and method for producing same, localized ablation device and localized ablation method, injection device and injection method, plasma-bubble jetting member, and therapeutic device and therapeutic method

Foreign code F210010339
File No. K03508US2
Posted date Feb 2, 2021
Country United States of America
Application number 202016884365
Gazette No. 20200337757
Date of filing May 27, 2020
Gazette Date Oct 29, 2020
Priority data
  • P2012-047053 (Mar 2, 2012) JP
  • P2013-003748 (Jan 11, 2013) JP
  • 201414382012 (Aug 29, 2014) US
  • 2013JP55703 (Mar 1, 2013) WO
Title Bubble jetting member and method for producing same, gas/liquid jetting member and method for producing same, localized ablation device and localized ablation method, injection device and injection method, plasma-bubble jetting member, and therapeutic device and therapeutic method
Abstract Through the use of a localized ablation device employing a bubble jetting member having a core formed from a conductive material, a shell part formed from an insulating material, covering the core and including a section extending from the tip of the core, and a space formed between the extended section of the shell part and the tip of the core, a process target can be treated in localized fashion and without inflicting damage. By further providing an outside shell part at the outer periphery of the shell part, bubbles onto which a solution containing an injection substance has been adsorbed can be ejected, and the injection substance can be introduced during localized ablation of the process target. Additionally, by including a pair of electrodes formed from a conducting material, for generating a plasma in an inert gas, a liquid flow passage through which a liquid flows, and a microscopic flow passage for flow of an inert gas, an inert gas containing a plasma, and bubbles of inert gas containing a plasma, the liquid flow passage and the microscopic flow passage connecting at the downstream side from a section in which plasma is generated in the microscopic flow passage, bubbles containing a plasma can be generated, and can maintain a plasma state even in liquid, whereby therapy of biological tissue can be effected with the plasma.
Outline of related art and contending technology BACKGROUND
Advances in biotechnology witnessed in recent years have been accompanied by increasing demand for localized process of cells and the like, involving making a hole in a cell membrane or wall, and removing the nucleus from the cell, or introducing DNA or other nucleic acid substance into the cell. Methods employing a number of localized process techniques (hereinafter sometimes referred to as “localized ablation methods”), such as contact process techniques using a probe, such as an electric scalpel or the like, or non-contact ablation techniques employing lasers or the like, are widely known. In particular, as a contact process technique using an electric scalpel, there has recently been proposed a technique for keeping the cauterization surface to one on the order of several micrometers, thereby minimizing the thermal invasion area and improving the resolution performance (see Non-patent Document 1).
Additionally, in the area of laser process, there have been notable breakthroughs in femtosecond lasers, and techniques for performing cell process (see Non-patent Document 2) and laser process techniques that minimize generation of bubbles in the liquid phase have been recently proposed.
However, in conventional contact process techniques employing a probe such as an electric scalpel, there was a tendency for the target to be burned away due to Joule heat generated by continuous high frequencies, resulting in significant roughness at the incision face and in surrounding tissue being significantly affected by thermal invasion due to heat (Problem 1); and rejoining and regeneration were difficult, due to denaturation of proteins and/or fragmentation of amide bonds (Problem 2). Moreover, with continuous process, adsorption onto the probe of cut proteins and/or adsorption of bubbles generated by heat resulted in the problem of marked degradation of the observation environment at the incision face, making high-resolution process difficult (Problem 3).
In non-contact process techniques employing lasers such as femtosecond lasers and the like as well, tissue surrounding the incision face was affected by localized bombardment with high-density energy, and particularly during process of a target in the liquid phase, generation of bubbles and the like due to heat generated during process made continuous process difficult (Problem 4). Another problem encountered during process of a target in the liquid phase with a laser such as femtosecond laser was difficulty in accessing the process target (Problem 5).
Meanwhile, electroporation, sonoporation techniques employing ultrasound, particle gun methods, and the like are widely known as localized physical injection techniques (injection methods) for introducing nucleic acid substances or the like into cells or the like. Electroporation is a technique in which an electrical pulse is imparted to a cell or the like, thus raising the cell membrane permeability in order to carry out injection; a technique for injection into a thin pliable cell membrane such as lipid bilayer membrane has been proposed (see Non-patent Document 3). In the area of sonoporation techniques employing ultrasound, it has been proposed to bombard bubbles with ultrasound to carry out injection by generating cavitation in a wide range of bubbles (see Non-patent Document 4). Additionally, the particle gun method is a technique involving depositing a substance to be introduced onto a particle, which is then physically shot into the target.
However, in conventional electroporation techniques, depending on the electrical field strength, there are limits as to how much the permeability of the cell membrane can be improved, making it difficult to inject into targets having stiff cell membranes or cell walls, instead of pliable lipid bilayer membranes (Problem 6); and due to restrictions regarding electrode placement and the like, localized injection at the intended site was difficult. Moreover, in sonoporation techniques employing ultrasound, it was difficult to focus the ultrasound, making it difficult to generate localized cavitation of bubbles and increase the resolution (Problem 7).
In injection methods that rely on the particle gun method as well, the problem of low efficiency of introduction, due to separation of the substance deposited on the particle surface occurring when the particle is shot in, was encountered (Problem 8). Additionally, the electroporation, sonoporation, and particle gun methods consume large amounts of substances for injection, making injection of costly substances difficult (Problem 9).
Plasmas are known to be able to contribute to killing malignant cells and healing biological tissue. However, in conventional plasma techniques, it was difficult to bring about a state that would generate a plasma in solution, and while a procedure of first generating a plasma a gas in proximity to the electrodes, and then using the generated plasma to generate bubbles including the plasma in solution, was adopted, the plasma state could not be sustained for an extended period, and it was moreover difficult to move the bubbles while maintaining a plasma state (Problem 10, see Non-patent Documents 5, 6).
Scope of claims [claim1]
1. A plasma bubble jetting member, comprising:
a pair of electrodes formed from a conducting material, and adapted for generating a plasma in an inert gas;
a liquid flow passage through which a liquid flows; and
a microscopic flow passage through which flow an inert gas, an inert gas containing a plasma, and a liquid containing bubbles of an inert gas containing a plasma;
the liquid flow passage and the microscopic flow passage connecting at a downstream side from a section in which the plasma is generated in the microscopic flow passage.

[claim2]
2. The plasma bubble jetting member according to claim 1, wherein the microscopic flow passage includes a plasma reservoir in which the section in which the plasma is generated is made larger than the rest of the microscopic flow passage.

[claim3]
3. A localized ablation device employing the plasma bubble jetting

[claim4]
2. ccording to claim 2.

[claim5]
4. A localized ablation method, comprising:
causing an inert gas to flow into the microscopic flow passage of the localized ablation device according to claim 3;
applying a high-frequency electrical pulse to the pair of electrodes to generate a plasma in the inflowing gas;
causing the inert gas containing the plasma to flow into a liquid in the liquid flow channel which connects to the microscopic flow passage, to generate bubbles containing plasma; and
processing a process target with the bubbles.

[claim6]
5. A therapeutic device employing the plasma bubble jetting member according to claim 2.

[claim7]
6. A therapeutic method, comprising:
causing an inert gas to flow into the microscopic flow passage of the therapeutic device according to claim 5;
applying a high-frequency electrical pulse to the pair of electrodes to generate a plasma in the inflowing gas;
causing the inert gas containing the plasma to flow into a liquid in a liquid flow channel which connects to the microscopic flow passage, to generate bubbles containing plasma; and
effecting therapy of biological tissue with the bubbles.

[claim8]
7. The plasma bubble jetting member according to claim 2, wherein the electrode is of a size at least sufficient to cover the plasma reservoir.

[claim9]
8. A localized ablation device employing the plasma bubble jetting member according to claim 7.

[claim10]
9. A localized ablation method, comprising:
causing an inert gas to flow into the microscopic flow passage of the localized ablation device according to claim 8;
applying a high-frequency electrical pulse to the pair of electrodes to generate a plasma in the inflowing gas;
causing the inert gas containing the plasma to flow into a liquid in the liquid flow channel which connects to the microscopic flow passage, to generate bubbles containing plasma; and
processing a process target with the bubbles.

[claim11]
10. A therapeutic device employing the plasma bubble jetting member according to claim 7.

[claim12]
11. A therapeutic method, comprising:
causing an inert gas to flow into the microscopic flow passage of the therapeutic device according to claim 10;
applying a high-frequency electrical pulse to the pair of electrodes to generate a plasma in the inflowing gas;
causing the inert gas containing the plasma to flow into a liquid in a liquid flow channel which connects to the microscopic flow passage, to generate bubbles containing plasma; and
effecting therapy of biological tissue with the bubbles.

[claim13]
12. A localized ablation device employing the plasma bubble jetting member according to claim 1.

[claim14]
13. A localized ablation method, comprising:
causing an inert gas to flow into the microscopic flow passage of the localized ablation device according to claim 12;
applying a high-frequency electrical pulse to the pair of electrodes to generate a plasma in the inflowing gas;
causing the inert gas containing the plasma to flow into a liquid in the liquid flow channel which connects to the microscopic flow passage, to generate bubbles containing plasma; and
processing a process target with the bubbles.

[claim15]
14. A therapeutic device employing the plasma bubble jetting member according to claim 1.

[claim16]
15. A therapeutic method, comprising:
causing an inert gas to flow into the microscopic flow passage of the therapeutic device according to claim 14;
applying a high-frequency electrical pulse to the pair of electrodes to generate a plasma in the inflowing gas;
causing the inert gas containing the plasma to flow into a liquid in a liquid flow channel which connects to the microscopic flow passage, to generate bubbles containing plasma; and
effecting therapy of biological tissue with the bubbles.

[claim17]
16. The plasma bubble jetting member according to claim 1, wherein the plasma bubble jetting member further comprises a substrate, and
the liquid flow passage and the microscopic flow passage are formed on the substrate.

[claim18]
17. A plasma bubble jetting member, comprising:
a pair of electrodes formed from a conducting material, and adapted for generating a plasma in an inert gas;
a liquid flow passage through which a liquid flows; and
a microscopic flow passage extending through a center flow direction axis and through which flow an inert gas, an inert gas containing a plasma, and a liquid containing bubbles of an inert gas containing a plasma along the center flow direction axis, wherein
the liquid flow passage connects and merges with the microscopic flow passage at a downstream side on the center flow direction axis from a section in which the plasma is generated in the microscopic flow passage.
  • Inventor, and Inventor/Applicant
  • YAMANISHI YOKO
  • SAKUMA SHINYA
  • KURIKI HIROKI
  • ARAI FUMIHITO
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
IPC(International Patent Classification)
Reference ( R and D project ) PRESTO Nanosystem and function emergence AREA
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