Treatment of the internal space using a plasma generating device

Abstract

The plasma delivery tip of a medical plasma generating device is configured to exclude potential contaminants during in-body cavity operation. In some embodiments, the delivery tip has a front chamber, which is optionally filled with the pressure of the ionized gas to prevent contamination. Some embodiments are provided with one or more internal and / or external valves, which are configured to prevent proximal entry of contaminants into the longitudinal position of the discharge electrode or full entry into the gas delivery lumen. In some embodiments, the expandable distal portion of the plasma delivery tip acts as a valve, which seals when closed and expands when opened to create an expanded front chamber into which the plasma is delivered.

Description

[0001] Related Applications

[0002] This application claims the benefit of priority to U.S. Provisional Patent Application No. 62 / 991,649, filed on March 19, 2020, under 35 U.S.C. § 119(e), which is incorporated herein by reference in its entirety.

[0003] This application is one of four co-filed applications, including PCT applications, with attorney docket numbers 85937, 85988, and 85987, the contents of each of which are incorporated herein by reference in their entirety.

[0004] Technical Field and Background Art

[0005] The present disclosure, in some embodiments, relates to the field of cold atmospheric plasma generation, and more particularly, to the delivery of cold plasma within a body cavity.

[0006] Plasma is a general term for a collection of ionized gases, typically including free electrons and ions, as well as neutral atoms and molecules, and often also free radicals. Plasma can be generated by gas discharge, which excites and ionizes gas atoms or molecules. In the past decade, there has been increasing interest in the applications of plasma. Some applications are based on dielectric barrier discharge (DBD) to generate low-temperature non-thermal plasma, or so-called "cold" plasma. Such cold plasma is low-ionized and non-thermal plasma generated under atmospheric pressure conditions. Cold plasma has been found to have a variety of uses in medicine and industry. SUMMARY OF THE INVENTION

[0007] According to one aspect of some embodiments of the present disclosure, a plasma delivery tip of a medical plasma generating device is provided, including: a gas delivery lumen defined within a circumferential wall and having a proximal-distal axis, and an ionized gas flow flowing along the proximal-distal axis towards a distal aperture of the gas delivery lumen; a discharge electrode that, when connected to a high voltage source, delivers a high voltage to the ionized gas flow; and a valve positioned to prevent contaminants from entering a longitudinal position of the discharge electrode along the proximal end of the proximal-distal axis.

[0008] According to some embodiments of the present disclosure, the valve, when closed, is also positioned to prevent liquid material from entering through the aperture.

[0009] According to some embodiments of the present disclosure, the valve is positioned within the gas delivery lumen and between the aperture and the discharge electrode.

[0010] According to some embodiments of the present disclosure, the valve includes a check valve that opens under the pressure of the ionized gas flow.

[0011] According to some embodiments of the present disclosure, the valve includes a drive valve that is driven separately from the pressure of the ionized gas flow.

[0012] According to some embodiments of the present disclosure, the hole of the gas delivery lumen is inclined with respect to the proximal - distal axis.

[0013] According to some embodiments of the present disclosure, the valve includes a flap valve, a slit valve, or a clapper valve.

[0014] According to some embodiments of the present disclosure, the valve is configured to deflect a plasma plume generated in the ionized gas flow by a high - voltage pulse by an angle that varies according to the opening degree of the valve.

[0015] According to some embodiments of the present disclosure, the plasma delivery tip includes an outer peripheral wall that surrounds and is radially spaced from the circumferential wall of the gas delivery lumen to define a gap, and the ionized gas is cleared through the gap after being delivered to the discharge electrode.

[0016] According to some embodiments of the present disclosure, the circumferential wall of the gas delivery lumen further defines a conduit through which the ionized gas is cleared after being delivered to the discharge electrode.

[0017] According to some embodiments of the present disclosure, when closed, the valve includes a folded pre - chamber of the gas delivery lumen positioned along the proximal - distal axis between the discharge electrode and the hole.

[0018] According to some embodiments of the present disclosure, the pre - chamber expands to have an inner diameter that is at least 1.5 times larger than the inner diameter of the pre - chamber in the folded configuration.

[0019] According to some embodiments of the present disclosure, the valve includes a calyx having one or more vanes connected to an exterior of the plasma delivery tip on its proximal side.

[0020] According to some embodiments of the present disclosure, when expanded to expose the hole of the gas delivery lumen, the plurality of vanes are separated from each other.

[0021] According to some embodiments of the present disclosure, the expanded pre - chamber defines the hole of the gas delivery lumen on a distal side of the pre - chamber. <L

[0022] According to some embodiments of the present disclosure, the folded pre - chamber includes a hard, sharp tip configured to penetrate tissue.

[0023] According to some embodiments of the present disclosure, the discharge electrode extends around at least a portion of a circumference of the gas delivery lumen.

[0024] According to some embodiments of the present disclosure, the discharge electrode is located within the gas delivery lumen and is surrounded by the ionized gas flow.

[0025] According to some embodiments of the present disclosure, an outer diameter of the plasma delivery tip is less than 5 millimeters.

[0026] According to one aspect of some embodiments of the present disclosure, a method of operating a plasma delivery tip is provided, including: contaminating an interior of a gas delivery lumen of the plasma delivery tip with a liquid; and operating the plasma delivery tip to generate plasma.

[0027] According to some embodiments of the present disclosure, a diameter of the lumen is less than 5 millimeters.

[0028] According to one aspect of some embodiments of the present disclosure, a method of operating a plasma delivery tip is provided, including: guiding the plasma delivery tip to an aqueous fluid in contact with a target surface; guiding plasma from the plasma delivery tip into the fluid; and redistributing reactive species guided in the fluid by the plasma to the target surface.

[0029] According to some embodiments of the present disclosure, plasma guided from the plasma delivery tip cannot access the target surface.

[0030] According to some embodiments of the present disclosure, the redistribution includes providing a fluid that replaces the aqueous fluid.

[0031] According to some embodiments of the present disclosure, the redistribution includes stirring the aqueous fluid.

[0032] According to some embodiments of the present disclosure, the redistribution includes redistributing the aqueous fluid to at least a partially dry region of the target surface.

[0033] According to some embodiments of the present disclosure, the method includes drying the at least partially dry region of the target surface.

[0034] According to one aspect of some embodiments of the present disclosure, a plasma delivery tip of a medical plasma generating device is provided, including: a gas delivery lumen defined within a circumferential wall and having a proximal-distal axis, and serving as a conduit for an ionized gas flow exiting through an aperture of the gas delivery lumen; and a discharge electrode positioned to receive a high voltage pulse from an electrical connection provided by a power supply of the plasma generating device and to deliver the pulse through a plasma generating region of the gas delivery lumen having a first inner diameter into the ionized gas flow; wherein the inner diameter of the aperture is greater than the first inner diameter.

[0035] According to some embodiments of the present disclosure, a distal portion of the circumferential wall remote from the discharge electrode is collapsible.

[0036] According to some embodiments of the present disclosure, the circumferential wall includes a thinner wall portion remote from the discharge electrode and a thicker wall portion within the plasma generating region.

[0037] According to some embodiments of the present disclosure, the thinner wall portion and the thicker wall portion are fixed relative to each other along the proximal-distal axis.

[0038] According to some embodiments of the present disclosure, the thinner wall portion and the thicker wall portion are relatively movable along the proximal-distal axis, with a maximum relative displacement of 50 millimeters or less.

[0039] According to one aspect of some embodiments of the present disclosure, a method of operating a plasma delivery tip is provided, including: guiding the plasma delivery tip to a target, with a closure member positioned to prevent contamination of an internal region of the delivery tip from extending along a discharge electrode remaining closed; opening the closure member; and operating the discharge electrode to generate cold plasma.

[0040] According to some embodiments of the present disclosure, the closure member includes a valve, and opening the valve includes delivering an ionized gas flow through the plasma delivery tip to press against the valve.

[0041] According to some embodiments of the present disclosure, the method includes pressing a distal side of the plasma delivery tip against a target before opening the closure member.

[0042] According to some embodiments of the present disclosure, the method includes delivering an ionized gas flow to the discharge electrode; wherein opening the closure member occurs prior to the delivery.

[0043] In accordance with one aspect of some embodiments of the present disclosure, a method of operating a plasma delivery tip is provided, including: guiding the plasma delivery tip to a target; pressing a distal side of the plasma delivery tip against a target; expanding a distal portion of the plasma delivery tip; and operating the plasma delivery tip to generate cold plasma.

[0044] According to some embodiments of the present disclosure, the expanding includes increasing a pressure within the distal portion while the distal portion is sealed against the target.

[0045] In accordance with one aspect of some embodiments of the present disclosure, a method of operating a plasma delivery tip in vivo is provided, including: guiding the plasma delivery tip to a location within a body lumen; blowing an ionizable gas together with a liquid from a distal aperture of a gas delivery lumen of the plasma delivery tip while guiding the plasma delivery tip within the body; and initiating ionization of the ionizable gas within the body lumen while the blowing is occurring.

[0046] In accordance with one aspect of some embodiments of the present disclosure, a medical plasma generating device is provided, including: a probe sized to be inserted into a selected portion of a body cavity and having a plasma generating distal tip including a discharge electrode and an aperture through which an ionizable gas flows; a plurality of balloons through at least one of which the probe extends; the plurality of balloons being sized and positioned to expand within the selected portion of the body cavity and seal the aperture therebetween.

[0047] According to some embodiments of the present disclosure, the plurality of balloons may be sized to seal a portion of a blood vessel lumen.

[0048] According to some embodiments of the present disclosure, the plurality of balloons may be sized to seal a portion of an intestinal lumen.

[0049] In accordance with one aspect of some embodiments of the present disclosure, a method of delivering plasma to a selected portion of a body cavity containing a liquid is provided, including: inserting a plasma delivery aperture of a plasma generating portion of a plasma delivery device to reach the selected portion of the body cavity; sealing the selected portion both distal and proximal to the aperture; removing liquid from the selected portion; and delivering plasma through the plasma delivery aperture to the selected portion.

[0050] According to some embodiments of the present disclosure, the sealing includes expanding balloons both distal and proximal to the aperture.

[0051] In accordance with one aspect of some embodiments of the present disclosure, a method of delivering plasma to an internal body region is provided, comprising: inserting a first probe and a second probe into the body region; and using the first and second probes: delivering an ionizable gas, ionizing the gas with a voltage to generate plasma, and purging the ionized gas; wherein the first probe is configured to perform no more than two of providing the gas, ionizing the gas, and purging the gas, and the second probe is configured to perform at least one of the remaining of providing the gas, ionizing the gas, and purging the gas.

[0052] In accordance with some embodiments of the present disclosure, the first probe is delivered to the body region through a flexible probe guided through a body cavity, and the second probe is delivered to the body region through a rigid probe inserted percutaneously.

[0053] In accordance with some embodiments of the present disclosure, the method further comprises delivering a supplementary fluid to the internal body region, the supplementary fluid comprising a molecular substance that reacts with the ionized ionizable gas.

[0054] In accordance with some embodiments of the present disclosure, at least one of the first and second probes is automatically positioned.

[0055] In accordance with one aspect of some embodiments of the present disclosure, a medical plasma generating device is provided, comprising: a probe sized to be inserted into a selected portion of a body cavity and having a plasma generating distal tip comprising a discharge electrode and a bore through which an ionizable gas flows; a switching valve positioned proximal to the plasma generating distal tip and operable to switch between delivering the ionizable gas to a lumen of the probe and delivering another gas to the lumen of the probe.

[0056] In accordance with one aspect of some embodiments of the present disclosure, a method of generating plasma in a body cavity is provided, comprising: generating plasma from an ionizable gas flowing through a bore of a plasma generating probe into the body cavity; stopping the flow of the ionizable gas; delivering a supplementary liquid to the body cavity through the bore of the plasma generating probe; and resuming the generating while the plasma generating probe remains within the body cavity.

[0057] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present disclosure, example methods and / or materials are described below. In case of conflict, the patent specification (including definitions) shall prevail. In addition, these materials, methods, and examples are illustrative only and not intended to be limiting.

[0058] As will be appreciated by one skilled in the art, aspects of the present disclosure may be embodied in a system, a method, or a computer program product. Accordingly, aspects of the present disclosure may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, microcode, etc.) or an embodiment combining software and hardware aspects, which may be collectively referred to herein as a "circuit", a "module", or a "system" (e.g., a method that may be implemented using "computer circuitry"). In addition, some embodiments of the present disclosure may take the form of a computer program product embodied in one or more computer-readable media and having computer-readable program code embodied thereon. Implementations of the methods and / or systems of some embodiments of the present disclosure may involve performing and / or completing selected tasks manually, automatically, or a combination of both. Additionally, for actual instruments and equipment of some embodiments of the methods and / or systems according to the present disclosure, several selected tasks may be implemented by hardware, software, or firmware and / or a combination thereof, such as using an operating system.

[0059] For example, according to some embodiments of the present disclosure, the hardware for performing selected tasks may be implemented as a chip or a circuit. As software, selected tasks according to some embodiments of the present disclosure may be implemented as multiple software instructions executed by a computer using any suitable operating system. In some embodiments of the present disclosure, one or more tasks performed by a method and / or by a system are executed by a data processor (also referred to herein as a "digital processor", referring to a data processor that operates on digital bit groups), such as a computing platform for executing multiple instructions. Optionally, the data processor includes volatile memory and / or non-volatile memory for storing instructions and / or data, e.g., a magnetic hard disk and / or a removable medium for storing instructions and / or data. A network connection may also be optionally provided. A display and / or a user input device, such as a keyboard or a mouse, may also be optionally provided. Here, any of these implementations are more generally referred to as examples of computer circuitry.

[0060] Any combination of one or more computer-readable media may be used in some embodiments of the present disclosure. The computer-readable media may be a computer-readable signal medium or a computer-readable storage medium. A computer-readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. More specific examples (a non-exhaustive list) of computer-readable storage media include: an electrical connection having one or more wires, a portable computer floppy disk, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM) or a flash memory, an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing. In the context of this document, a computer-readable storage medium may be any tangible medium that can contain or store a program for use by or in connection with an instruction execution system, apparatus, or device. A computer-readable storage medium may also contain or store information for use by such a program, such as, for example, data structures, which are recorded by the computer-readable storage medium so that a computer program can access it, such as, one or more tables, lists, arrays, data trees, and / or other data structures. Herein, a computer-readable storage medium that records data in a retrievable digital bit group form is also referred to as a digital memory. It should be understood that in some embodiments, if the computer-readable storage medium is not inherently read-only and / or is in a read-only state, the computer-readable storage medium may also optionally be used as a computer-writable storage medium.

[0061] Herein, a data processor is said to be "configured" to perform data processing operations as long as it is coupled to a computer-readable medium so as to receive instructions and / or data therefrom, process them, and / or store the processing results in the same or another computer-readable medium. The processing performed (optionally on data) is specified by instructions, and the result is that the processor operates in accordance with the instructions. The act of processing may be additionally or alternatively referred to by one or more other terms; for example: comparing, estimating, determining, calculating, identifying, associating, storing, analyzing, selecting, and / or transforming. For example, in some embodiments, a digital processor receives instructions and data from a digital memory, processes the data according to the instructions, and / or stores the processing results in the digital memory. In some embodiments, "providing" the processing results includes conveying, storing, and / or presenting one or more of the processing results. Optional presentation includes displaying on a display, indicating by sound, printing on a printout, or presenting the results in a form accessible to human sensory capabilities.

[0062] A computer-readable signal medium may include a propagated data signal that contains computer-readable program code therein, for example, in a baseband or as part of a carrier wave. Such a propagated signal can take any of a variety of forms, including but not limited to electromagnetic, optical, or any suitable combination thereof. A computer-readable signal medium can be any computer-readable medium that is not a computer-readable storage medium and can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.

[0063] The program code and / or data used thereby included on a computer-readable medium can be conveyed using any suitable medium, including but not limited to wireless, cable, fiber optic cable, radio frequency, etc., or any suitable combination of the foregoing.

[0064] The computer program code for performing operations for some embodiments of the present disclosure can be written in any combination of one or more programming languages, including object-oriented programming languages such as Java, Smalltalk, C++, or the like, and conventional procedural programming languages such as the "C" programming language or the like. The program code can execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer, or entirely on the remote computer or server. In the latter case, the remote computer can be connected to the user's computer through any type of network connection, including a local area network (LAN) or a wide area network (WAN), or to an external computer (e.g., through the use of a network service provider's network).

[0065] Some embodiments of the present disclosure will be described below with reference to the flowcharts and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the present disclosure. It will be understood that each part of the flowcharts and / or block diagrams, and combinations of parts in the flowcharts and / or block diagrams, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions executed by the computer processor or other programmable data processing apparatus create a means for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks.

[0066] These computer program instructions can also be stored in a computer-readable medium that can direct a computer, other programmable data processing apparatus, or other devices to operate in a particular manner, such that the instructions stored in the computer-readable medium produce an article of manufacture including instructions for implementing the functions / acts specified in the flowchart and / or block or blocks of the block diagram.

[0067] The computer program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other devices to cause a series of operational steps to be performed on the computer, other programmable apparatus, or other devices to produce a computer-implemented process such that the instructions executed on the computer or other programmable apparatus provide a process for implementing the functions / acts specified in the flowchart and / or block or blocks of the block diagram. BRIEF DESCRIPTION OF THE DRAWINGS

[0068] Some embodiments of the present disclosure are described herein by way of example only and with reference to the accompanying drawings. Now specifically referring to the drawings in detail, it is emphasized that the details shown are exemplary and for the purpose of illustrative discussion of embodiments of the present disclosure. In this regard, the description in conjunction with the drawings will be apparent to those skilled in the art as to how the embodiments of the present disclosure may be practiced.

[0069] In the drawings:

[0070] Figures 1A - 1B schematically depicts a plasma treatment device according to some embodiments of the present disclosure;

[0071] Figure 2A schematically depicts a plasma delivery tip including a front chamber according to some embodiments of the present disclosure, the front chamber providing a longitudinal separation between a plasma generation site near a discharge electrode and an external volume surrounding the plasma delivery tip;

[0072] Figure 2B -2E schematically depicts a valve configuration of a plasma delivery tip according to some embodiments of the present disclosure, which uses an ionized gas flow flowing through an inner cavity around which a circumferentially positioned discharge electrode extends to generate plasma;

[0073] Figures 3A - 3F schematically depicts a valve configuration of a plasma delivery tip according to some embodiments of the present disclosure, which uses an ionized gas flow flowing through an inner cavity in which a discharge electrode is located to generate plasma;

[0074] Figures 4A - 4C schematically depicts a distal view of different valve designs according to some embodiments of the present disclosure;

[0075] Figures 5A - 5B schematically depicts, according to some embodiments of the present disclosure, in the folded ( Figure 5A ) and expanded (Figure 5B )View of a deployable tip plasma delivery tip;

[0076] Figure 5C Schematic cross-sectional views of a deployable tip plasma delivery tip in folded and deployed configurations, in accordance with some embodiments of the present disclosure;

[0077] Figure 5D Schematic cross-sectional views of a deployable tip plasma delivery tip in folded and deployed configurations, in accordance with some embodiments of the present disclosure;

[0078] Figure 5E Schematic cross-sectional views of a deployable tip plasma delivery tip in folded and deployed configurations and including a calyx, in accordance with some embodiments of the present disclosure;

[0079] Figure 5F Schematic representation of the deployment of a self-expanding distal end from an introducer, in accordance with some embodiments of the present disclosure;

[0080] Figures 6A - 6C Schematic representation of an access mode for delivering plasma to a plasma treatment target located within a lung, in accordance with some embodiments of the present disclosure;

[0081] Figure 6D There is provided a detailed view of an example of a plasma delivery configuration corresponding to Figure 6C in accordance with some embodiments of the present disclosure;

[0082] Figure 6E is a schematic flow chart of a method for performing plasma treatment within a body cavity, in accordance with some embodiments of the present disclosure;

[0083] Figures 7A - 7C Schematic representation of applying plasma treatment to a target within a solid organ, in accordance with some embodiments of the present disclosure;

[0084] Figures 8A - 8B schematically represent applying plasma treatment to a target within the urinary tract, in accordance with some embodiments of the present disclosure;

[0085] Figure 9 is a schematic flow chart of a method for delivering plasma to a target within a body cavity, in accordance with some embodiments of the present disclosure;

[0086] Figure 10 is a schematic flow chart of a method for delivering plasma to a target within a body cavity, in accordance with some embodiments of the present disclosure;

[0087] Figure 11 is a schematic flow chart of a method for delivering a plasma-activated fluid to a target surface within a body cavity, in accordance with some embodiments of the present disclosure;

[0088] Figure 12 is a schematic flow chart of a method for delivering a plasma-activated fluid to an inaccessible target surface within a body cavity according to some embodiments of the present disclosure;

[0089] Figures 13A - 13B schematically represents a plasma delivery device according to some embodiments of the present disclosure, which operates to deliver plasma within a lumen space established by the expansion of a balloon; and

[0090] Figure 13C is a schematic flow chart of a method for using Figures 13A - 13B a plasma delivery tip according to some embodiments of the present disclosure. DETAILED DESCRIPTION

[0091] The present disclosure, in some of its embodiments, relates to the field of cold atmospheric plasma generation and, more particularly, to the delivery of cold plasma within a body cavity.

[0092] OVERVIEW

[0093] One aspect of some embodiments of the present disclosure relates to a cold (non-thermal) plasma generation device configured to direct within a body cavity and / or resist the entry of contaminants when delivering plasma to living tissue within a body cavity. The plasma generation device is configured to provide cold (non-thermal) plasma to living tissue under medical-grade temperature, safety, and sterility conditions.

[0094] Cold plasma has potential therapeutic effects. For example, it may disrupt and / or trigger the disruption of tumor cells and / or pathogens such as viral particles, bacteria, and / or fungi.

[0095] The mechanism of the therapeutic effect is an area of ongoing research. One proposed mechanism of action involves free radicals (such as OH - ), such as the oxidative stress caused by free radicals. The treatment can utilize the different sensitivities of normal tissue and the target to tumors and / or pathogens to free radicals. The treatment effect may depend on the interaction between the parameters of the target (e.g., surrounding fluid, target size, and / or target type) and the parameters of the delivered plasma (e.g., generated ionized species, their concentration, and / or ratio). The parameters of the sequentially delivered plasma may be affected by the parameters of plasma generation (such as ionization medium composition and / or electrical parameters) and the parameters of the plasma plume itself (such as geometry, containment, flow, and / or quenching).

[0096] Here, "plasma" and "plasma plume" refer to cold plasma (e.g., plasma at a temperature of 50 °C or below, preferably delivered at a temperature below body temperature, e.g., in the range of approximately 20 °C - 30 °C). Cold plasma is typically delivered under conditions of near atmospheric pressure and is thus also referred to as "cold atmospheric plasma" or CAP (cold atmospheric plasma).

[0097] In some embodiments, the tissue target to which the cold plasma is delivered is inside a living body. Optionally, the target is outside the living body, and optionally, the target is not part of a living body. For example, the target can be a calibration target, e.g., a target for characterizing the plasma generated under different settings of a plasma delivery device, optionally including different parameter settings of the plasma delivery tip; e.g.: different dielectric barrier thicknesses, different gas delivery lumen diameters, and / or different discharge electrode widths. Additionally, the target is an analysis target; e.g., a target for in vitro and / or ex vivo testing of the cold plasma effect (e.g., under different parameter settings of the plasma delivery tip) on one or more types of, e.g.: tumor cells, pathogen cells, virus particles, healthy cells, and / or tissue samples.

[0098] Cold plasma is generated in a non - equilibrium state relative to its environment, and its ionization state rapidly decays as a result of interactions between charged particles, interactions with other particles in the ionized gas, and / or interactions with molecules in the environment.

[0099] In some embodiments, a cold plasma plume (e.g., approximately 1 - 20 millimeters in length) is generated by a high - voltage discharge electrode operating in an ionized gas environment created near the target. Cold plasma has the characteristic of a non - equilibrium state and is weakly ionized. It is estimated that for some cold plasmas, the ionization is approximately (a multiple of about 10) one - millionth and / or 10 11 -10 13 electrons / cm 3 . Through the flow of the ionizable gas, the generated plasma is carried towards the target.

[0100] A series of potential problems are associated with the contamination of the plasma generation and / or delivery components of a medical cold plasma delivery system.

[0101] Body cavities are moist places that carry liquids with solutes (such as electrolytes and / or macromolecules) and / or suspended particles (such as cells and / or cell debris).

[0102] The presence of some water molecules may help enhance the treatment effect: e.g., when the target itself is wet, the OH generated by the plasma -Free radicals may be enhanced, or gaseous H2O may be intentionally introduced into the ionized gas mixture itself. Plasma delivered to a liquid (such as an aqueous liquid) may "activate" the liquid, such that ionic and / or molecular species within the liquid itself become more reactive. The liquid itself can then serve as a medium allowing for further redistribution of these reactive species, delivering a therapeutic effect to a treatment target.

[0103] However, excessive moisture in the wrong place is potentially harmful for plasma generation and / or propagation. For example, if a plasma electron loses energy when generating an OH - radical and it cannot reach the target, then it can no longer treat the target itself. Moisture may interfere with the voltage field strength and / or clog the gas delivery lumen. This can result in diminished and / or less reliable plasma generation.

[0104] Moisture (water) can be in liquid or gaseous form. Of particular note is liquid moisture within the lumen of the plasma delivery tip. This can affect the electric field strength encountered by the ionized gas in the plasma generation region and / or induce its quenching once the plasma is generated. Evaporated or otherwise emptied liquid can also pose potential problems as it may contain electrolytes and / or suspended particles that are left as residues, contaminating, quenching, and / or otherwise affecting plasma generation and / or delivery.

[0105] Once the ionized gas begins to flow, gaseous water (such as humidity) is easily blown away - but gaseous water can also intrude and condense to form droplets. For example, cold plasma generated at room temperature can cool water-saturated body temperature gas enough to cause condensation.

[0106] Accordingly, it is a potential advantage to construct and operate a plasma delivery tip to exclude the intrusion of moisture in liquid and / or gaseous form.

[0107] In some embodiments, the plasma generation site and "fore chamber" of the plasma delivery tip include a post-generation site compartment having an open distal aperture that is small: for example, the longitudinal extent (along the proximal-distal axis) is between about 1 millimeter and 10 millimeters, and the outer diameter is about 15 millimeters or less, about 10 millimeters or less, about 5 millimeters or less, about 4 millimeters or less, or about 3 millimeters or less. The corresponding inner diameter is smaller; an optional range is less than 1 millimeter (e.g., 0.4 - 0.8 millimeter), or in larger body cavities can reach about 3 - 5 millimeters, or can reach a diameter range of any of the listed outer diameters, minus an overall double-wall thickness of about 0.5 - 2 millimeters. Thus, a relatively small amount of liquid contamination (possibly a microliter of liquid, or even less) can significantly disrupt the therapeutic effect at the target site.

[0108] In some embodiments, the inner diameter of the plasma delivery tip is further expandable, e.g., by 1.5 times, 2 times, 3 times or more (e.g., compared to the folded diameter of the plasma delivery tip and optionally compared to the diameter of the gas delivery tube at the longitudinal position of the discharge electrode). Optionally, the expandable portion of the plasma delivery tip is tapered when expanded (and widens at its distal end). This potentially increases the target area while allowing treatment via the plasma delivery probe. However, it includes the potential risk of increased contact liquid contamination. When refolded, the intruding liquid may be trapped and / or spread into the plasma delivery tip.

[0109] In these respects, it should also be noted that wetting and surface tension phenomena are potentially important considerations in managing liquid entry. For example, liquids with high surface tension (such as many aqueous liquids) are not necessarily prone to intrusion into small pores unless the pressure differential is large enough to overcome the surface tension. Conversely, wetting (e.g., accompanied by the process of capillary action) can be debilitating.

[0110] In some embodiments, the plasma delivery tip is constructed using hydrophobic materials and / or coatings, potentially preventing wetting and / or capillary action and enhancing the contamination exclusion performance associated with surface tension phenomena. However, it should be noted that high electric field conditions (used, e.g., to generate plasma) have the potential to disrupt surface tension phenomena through electro-wetting. The plasma itself may also cause surface modifications that affect hydrophobicity.

[0111] In some embodiments, contamination exclusion includes using the flow of the ionization gas itself to fill, pressurize, and / or dry the space within the plasma generation probe. As long as the pressure is maintained, it is possible to prevent the entry of low-pressure fluids. In some embodiments, alternative or additional protection against the entry of contaminants is provided.

[0112] In some embodiments, contamination exclusion includes a closure (e.g., a sealing member) that is capable of opening reversibly or irreversibly to allow the delivery of plasma. In some embodiments, the plasma delivery tip is valved (i.e., the closure includes a valve), and the valve is located between the distal aperture of the plasma delivery tip and the device including the discharge electrode at the site where plasma is generated. Optionally, the valve includes the distal aperture itself. In some embodiments, a closure structure is provided that is distally located beyond the distal aperture, e.g., in the form of a "calyx" that, when opened, exposes the distal aperture behind and / or below it. In some embodiments, a portion of the plasma delivery tip is interchangeable between folded and expanded configurations, where the folded configuration resists or prevents the intrusion of contamination.

[0113] Such blocking structures provide potential advantages in the following situations:

[0114] · Transient high pressure; for example, encountering an obstacle during the guiding process, which may force contaminants back to the delivery tip.

[0115] · Risk of solid particle ingress - can occur even at high pressures; for example, if the flow rate itself is very low.

[0116] · Strict dimensional limitations. Expansion of a small space may pose a risk of tissue damage, such as tearing. Limitations on the lumen cross-section of the device that can be introduced into such a space prevent the introduction of a gas evacuation lumen to counteract the expansion.

[0117] · Not all in-vivo cavity spaces are necessarily suitable for continuous gas perfusion even when gas evacuation is carried out simultaneously; for example, due to the risk of embolism or tissue damage.

[0118] Here, "evacuating" the gas means evacuating the gas through a pipe dedicated to such evacuation after the gas has completed its initial function; for example, participating in generating a plasma plume, opening a valve, and / or drying or moistening the lumen wall.

[0119] In some embodiments, actuation (e.g., opening a valve or expanding / expansion structure) is performed using the pressure from the flow of the ionized gas itself. In some embodiments, the actuation is controlled separately, for example, using a mechanical actuator, piezoelectric effect, or another active actuation method. Optionally, it can be controlled separately but coordinated, for example, opening a piezoelectrically actuated valve in coordination with the delivery of the ionized gas. The coordination can be performed in an "open loop" manner (e.g., sending commands at coordinated times), and / or using sensing (e.g., pressure buildup and / or pressure loss).

[0120] Optionally, a structure that combines to provide a valve and / or close the distal hole of the plasma delivery tip is provided, for example, optionally providing a calyx (distal to the distal hole of the gas delivery cavity) and a valve (proximal to the hole) together.

[0121] Optionally, the valve and / or the structure that closes the distal hole of the plasma delivery tip has an auxiliary function. For example, the distal end of the plasma delivery tip may be soft and / or blunt, so it can serve as a non-traumatic tip (e.g., at least partially folding, deflecting, and / or deforming when sufficient pressure is applied). Or, in some embodiments, the distal end of the plasma delivery tip can be hard and / or sharpened so that it can dissect and / or penetrate tissue. For example, the distal end of the plasma delivery tip is optionally tilted to provide a trocar-like tip. In some embodiments, the distal end of the plasma delivery tip (when closed) is gathered into a sharpened point configured to penetrate tissue, such as a needle.

[0122] A complementary method of managing contaminants by exclusion is to remove moisture from the work area to remove water molecules and / or control their concentration. In some embodiments, the plasma delivery tip has a gas scavenging lumen that is optionally operable to scavenge the ionized gas as it is being delivered. When gas scavenging is performed to remove gas from the forechamber corresponding to the target surface, this may help to dry and / or balance (e.g., coordinate with the water-containing species delivered in the ionized gas) the moisture level of the target surface and / or the inner surface of the forechamber. This may help to redistribute the activation fluid of the active component to the treatment target surface. For example, a target surface that is too dry or too wet may absorb and / or produce different active species (e.g., with lower efficiency) compared to a moderately moist target surface. Optionally, the target surface is dried with an ambient liquid and then wetted with an active liquid. The initial drying of the surface may promote the redistribution of the activation fluid, e.g., due to the interaction of the wet surfaces, which facilitates the migration of the fluid.

[0123] Optionally, the removal of contaminants, moisture, and liquid is performed by reversing the direction of flow within the gas delivery lumen, which is typically operated to provide ionized gas from a source. Optionally, the gas delivery lumen alternates between generating plasma and performing suction. In embodiments that include a valve, the valve is optionally forced open by a method other than internal pressure. To avoid inhaling new contaminants, a clean gas supply is optionally provided to the distal end of the plasma delivery tip (e.g., through another lumen of the plasma treatment device; e.g., the scavenging lumen, which can serve as an evacuation conduit for the spent ionized gas). The supply can be an excess suction. In embodiments that include a valve, the supply can be provided through a hole located near the valve so that the valve can remain closed, or if the valve is open, it will open with a pressure to resist further entry of contamination. Thus, in some embodiments, the valve is placed in a position that protects the multiple lumens from contamination when closed.

[0124] In some embodiments, the plasma delivery tip allows at least partial contamination (e.g., by liquid) inside the plasma delivery tip and then operates to generate plasma within the body lumen. Optionally, the contaminants are removed (e.g., by gas flow) before plasma generation begins. Optionally, the contaminants are confined to the inner portion of the plasma delivery tip, which is isolated from the functionally sensitive region (e.g., the plasma generation site) by a valve or other barrier. In some embodiments, the inner diameter of the plasma delivery tip is less than 5 mm, less than 3 mm, or less than 1 mm; e.g., small enough that even minor contamination (e.g., contamination caused by droplets, or optionally, even droplets formed by condensation of gas within the body lumen) can easily and significantly impair plasma generation.

[0125] One aspect of some pre-disclosed embodiments relates to the use of plasma-activated fluids to distribute active substances within body cavities.

[0126] In some embodiments, plasma-activated liquids (e.g., aqueous solutions) are used to help distribute the therapeutic effects of the plasma over a larger area than might be directly contacted by the plasma plume. This is a potential advantage in increasing the treatment surface area (e.g., compared to the surface area directly impacted by the plasma plume), and / or allowing the active substances to reach surfaces that the plasma plume cannot directly treat.

[0127] Electrons and / or ionized species in the plasma plume have the potential to enter the surrounding fluid and / or interact with substances in the fluid that contacts the plasma plume, thereby "activating" the fluid. The then-activated fluid contains active (possibly relatively short-lived) substances that may be able to readily modify the molecules they contact, including cellular molecules. Thus, the activated fluid can propagate the plasma-induced therapeutic effects. Accordingly, there is a potential advantage in using plasma-activated fluids (gases and / or liquids) for the redistribution of fluid-based plasma effects.

[0128] Due to their short lifetimes, the most active substances in plasma-activated fluids tend to rapidly decay in concentration after their initial formation. There is a potential advantage in activating the plasma-activated liquid at the treatment site to reduce transport delays during which potential therapeutic effects can be diminished by the loss of active substances.

[0129] In addition, there is a potential advantage in controlling the movement and / or geometry of the active fluid that distributes the active components. For example, a fluid in the form of a thin liquid layer can provide a shorter and / or more controlled path to the target. The fluid spreading from the point of introduction (e.g., under pressure and / or surface interactions) may carry the active substances and cause them to spread faster than they otherwise would, e.g., by diffusion.

[0130] Here, the term "activating fluid" refers to a fluid (however introduced) that encounters a plasma plume outside the plasma plume formation region. Such fluids may include gases and / or liquids. The fluid optionally includes gas-phase species that condense into a liquid phase and / or liquid-phase species that evaporate into a gas phase. Prior to being activated, these fluids are referred to herein as "ambient" fluids. Ambient fluids may include fluids that pre-exist and / or are naturally introduced into the region near the target (such as body fluids, inspired atmospheric gases, etc.). Additionally, ambient fluids include fluids that are artificially introduced near the target. Optionally, artificial introduction is performed through a lumen separate from the gas delivery lumen. For example, any of the gas scavenging lumens described herein may be operated selectively or additionally as a lumen for fluid introduction. If a fluid is being introduced by the gas delivery lumen itself when the plasma reaches the location where the plasma is generated, then that fluid may initially be considered "part of the plasma plume" here. However, the gas delivery lumen may also deliver ambient fluid. For example, during periods when no plasma is being generated, an ionized gas (or another fluid) may be selectively discharged into the surrounding environment, where it becomes the medium of the ambient fluid and may later be activated. "Used" or "spent" ionized gas (even if initially part of the plasma plume itself) may be selectively re-activated upon re-encountering the current plasma plume and thus can also serve as an "ambient" fluid.

[0131] Activated gaseous fluids have the potential advantage of producing a rapid and / or widespread distribution of active species; however, gaseous fluids also tend to be associated with a relatively high volume-to-surface area ratio (unless this ratio is restricted by the shape of the space surrounding the gaseous fluid). Activated liquids (such as aqueous liquids) have the potential advantage of forming a thin film on the surface, which can reduce the volume-surface ratio. This may result in a more efficient transfer of active species across the target surface.

[0132] Compared to the kinetics of direct gas-phase condensation, the re-distribution of active species in an aqueous solution into semi-aqueous targets such as cell tissues may also have kinetic advantages. For example, the disruption and / or mixing resulting from "injecting" a gas plasma into a liquid may accelerate the kinetics of the initial condensation / generation of active species in the liquid, after which the activated liquid serves as a medium to re-distribute the active species across the target surface.

[0133] One aspect of some embodiments of the present disclosure relates to supplementing the supply of atomic and / or molecular species, alternating with a primary ionized gas. In some embodiments, the targeted effect of the plasma on the treatment target involves molecular species (herein referred to as supplementing species) that are not found in the ionized gas that has been selected to generate the plasma itself. For example, the ionized gas may consist of helium, neon, and / or argon, but the plasma-mediated effect may involve ions of other molecular species, such as those produced by oxygen, nitrogen, carbon dioxide, argon, and / or water. In the case where plasma treatment is applied to an open atmospheric surface, the molecular reagents that produce these ionic species are typically available from atmospheric molecules. However, in a closed space, such as a human body cavity, these reagents may not be present, or may be depleted before the treatment is complete. However, providing these reagents together with the ionized gas may change (increase) the breakdown threshold voltage of the gas. This may terminate plasma generation; and / or require an increase in the level of the supply voltage beyond those that may be optimal from other considerations, such as the power dissipation rate and / or the overall voltage tolerance of the device components.

[0134] In some embodiments of the present disclosure, the supplementing species are supplied alternately with the cycles of the ionized gas; for example, for a period of about 20 seconds, the gas supply is supplemented with the supplementing species for 1 - 5 seconds. The duty cycle of the ionized gas delivery can be between, for example, approximately 70% - 99% of the time. The remaining time in the duty cycle is used to provide the supplementing molecular species. In some embodiments, the valves are driven by a controller that also sets the time and duty cycle of the valve operation.

[0135] In some embodiments, the cycle time for switching the duty cycle between the fluid carrying the supplementing species and the ionized gas is reduced from several seconds for a full cycle to about one second or even shorter, for example, every 500 milliseconds, 200 milliseconds, or 100 milliseconds. Optionally, the duty cycle is short enough such that two or more boluses of at least one different fluid composition are present in the lumen leading to the plasma delivery tip simultaneously with one or more boluses of a different fluid composition. Except for possible mixing at their boundaries, the central regions of the different boluses remain unmixed, at least until they pass through the discharge electrode and / or enter the environment. Reducing the cycle time has the potential advantage of improving the homogenization of the ionized gas and the supplementing species and / or reducing the interval for adjusting the fluid / gas input to the system to balance the relative amounts of the ionized gas and the supplementing species. Optionally, the homogenization is assisted by using baffles.

[0136] In some embodiments, control of the power delivery is implemented to coincide with the passage of the ionized gas mass through the discharge electrode and is turned off when other fluids pass through the discharge electrode. In some embodiments, this can be accomplished by placing the control of the switch and the electrical output under the command of a single controller; or by having multiple controllers communicate with each other and / or operate using a common set of operating parameters; for example, parameters stored in a computer memory and / or electrical values set by controls such as variable resistors.

[0137] In some embodiments of the present disclosure, the alternation of fluids includes delivering a liquid, such as brine, through the ionized gas delivery lumen. While switching back to the ionized gas, a dry gas may be optionally and / or prior thereto delivered through the gas delivery lumen to assist in cleaning the liquid. Injecting the liquid through the ionized gas delivery lumen can serve as a method of cleaning the lumen and / or as a method of helping to ensure that there is no backflow into the lumen. The liquid used for cleaning and / or maintaining cleanliness is optionally injected at selected times (rather than in cycles) or at any suitable cyclic intervals, for example, as in the general case of alternating liquid injection as described.

[0138] In some embodiments, the gas delivery of supplementary substances also ensures that the gas discharged from the plasma application area itself has too high a breakdown threshold and will not inadvertently be converted into plasma. This can be important, for example, when the lumen of a probe is cleared using a gas, and the lumen of the probe runs together with the electrical conductor used to generate plasma at the tip of the probe. In some embodiments, the supplementary gas supply is made often enough and in sufficient quantity to maintain a sufficient margin of breakdown voltage, a voltage higher than the voltage carried by the conductor located near the gas exhaust duct.

[0139] One aspect of some embodiments of the present disclosure relates to delivering plasma to a lumen space that is normally or potentially filled with liquid, such as a blood vessel, a gastrointestinal segment, or a urinary tract segment. Being fully immersed in an aqueous solution is generally not suitable for generating plasma. Therefore, in order to bring plasma to an area within a liquid-filled body cavity, such as a blood vessel, it is a potential advantage to provide a system that can create a volume within the body cavity that is fluidly isolated from an adjacent volume of fluid, empty it, perform plasma treatment, and then, if necessary, fill the isolated area with liquid (removing bubbles that may cause embolisms), and the isolated volume is released again.

[0140] In some embodiments, the plasma delivery tip has an expandable structure, such as a balloon, that can be inflated or otherwise expanded to create fluid isolation and then deflated after treatment is complete to establish a fluid seal with the body cavity in a reversible manner.

[0141] In some embodiments, evacuation of the area isolated for treatment is accomplished by pushing gas into the area while allowing existing liquid to drain out accordingly. Optionally, suction pressure aids drainage. Optionally, a wash liquid is used during the drainage process, for example, replacing a viscous liquid (such as blood) with a lower viscosity liquid (such as saline), and then introducing gas to generate plasma. The gas can be a dry gas and may also assist in removing liquid from the isolated volume.

[0142] Generally, a system for isolating a treatment area includes a distal sealing element and a proximal sealing element with a hole therebetween through which plasma and / or ionized gas is introduced. Both sealing elements can be part of the plasma delivery tip itself; or one or both of them can be introduced and positioned separately.

[0143] Before explaining in detail at least one embodiment of the present disclosure, it must be understood that the application of the present disclosure is not necessarily limited to the structural details and component and / or method arrangements described below and / or illustrated in the figures. The features described in the present disclosure, including the features of the present disclosure, can be implemented in other embodiments or practiced or implemented in various ways.

[0144] Plasma treatment device

[0145] Now refer to Figures 1A - 1B , which is a schematic diagram showing the configuration of a plasma treatment device 55 according to some embodiments of the present disclosure.

[0146] In some embodiments, the plasma treatment device 55 includes a high-voltage power controller 60 and an ionizable gas supply 61 interconnected with a plasma probe assembly 62. The high-voltage power controller 60 supplies an ionization voltage to the plasma probe assembly 62 through a cable 71 (which can be, for example, a coaxial cable or another electrical conduit having a controlled impedance and shielding along its length). The ionizable gas supply 61 supplies an ionizable gas to the plasma probe assembly 62 through a pipeline 72. The gas supply can include, for example, one or more inert gases such as neon, argon, or helium; and / or other gases suitable for ionization into a plasma plume. Optionally, the cable 71 and the pipeline 72 are integrated into a single cable unit connecting the plasma probe assembly 62. Optionally, the high-voltage power controller 60 and the ionizable gas supply 61 are integrally installed.

[0147] The plasma probe assembly 62 optionally includes a handle 80. The handle 80 is optionally equipped with controls 81, 82 for controlling the drive of the probe catheter 73 and / or the plasma delivery tip 66, for controlling the functions of the power controller 60, and / or for controlling the delivery of the ionizable gas from the gas supply 61. The plasma probe assembly 62 optionally integrates the power function and the gas delivery function into the probe catheter without using a dedicated handle. In some embodiments, the probe catheter 73 includes both a lumen for delivering the ionized gas and a high voltage (e.g., a continuation of the cable 71 and the line 72).

[0148] In some embodiments of the present disclosure, the probe catheter 73 and the plasma delivery tip 66 are sized and otherwise configured (e.g., safety configured) to deliver cold plasma to an in vivo location. In some embodiments of the present disclosure, the plasma delivery tip is configured to access a target area within the body through a lumen and / or an aperture, such as: about 15 millimeters or less, about 10 millimeters or less, about 5 millimeters or less, about 4 millimeters or less, or about 3 millimeters or less. The diameter of the gas delivery lumen is optionally between 0.4 millimeters and 8 millimeters, and the lumen delivers the ionized gas into the plasma of the plasma delivery tip and / or the ionized gas itself exits the plasma delivery tip as a plasma plume. The length of the portion of the plasma delivery tip that generates and forms the plasma plume is optionally between about 4 millimeters and 30 millimeters. A longer length may optionally use a correspondingly higher discharge voltage to prevent dielectric breakdown.

[0149] Figure 1A The plasma probe assembly 62 is shown in an "independent" configuration, e.g., a configuration that can itself be used as a guiding catheter to reach an in vivo target. However, it should be understood that in some embodiments, the plasma probe assembly 62 is optionally used with another device; e.g., through the working channel of an endoscope or inserted into a cavity through a separate catheter. The plasma probe assembly 62 is illustrated as including a flexible probe catheter 73, however, it should be understood that the probe catheter 73 is optionally rigid, optionally straight or curved. The probe catheter 73 can be selected to be any suitable length to reach its target.

[0150] Some embodiments of the present disclosure are described as including a sheath or overtube having a lumen through which an element of the plasma delivery tip moves forward. Optionally, the sheath is part of the probe catheter 73. Optionally, the sheath is provided as a lumen of a device into which the plasma probe assembly is inserted, e.g., the working channel of an endoscope or a separately provided catheter. Embodiments shown and / or described without a sheath may optionally be provided and / or operated using a sheath. Conversely, embodiments described using a sheath may optionally be provided and / or "sheathless" operated, although specific features that rely on the sheath (e.g., using a portion of its lumen space as a gas and / or plasma return path) may subsequently not be available.

[0151] The power delivered to the plasma plume through the plasma delivery tip 66 can optionally range from 0.1 - 10 watts, 0.1 - 5 watts, or 1 - 2 watts (e.g., about 1.5 watts). The current through the plasma delivery tip can optionally range from about 5 - 20 milliamperes (e.g., about 8 milliamperes). The voltage used to generate the plasma can optionally range from about 750 - 850 volts (at radio frequency). Optionally, the voltage is higher, e.g., up to about 1000 volts or 1600 volts. The ionization flow rate through the plasma delivery tip 66 (at approximately atmospheric pressure) can optionally range between about 0.1 liters per minute to about 9 liters per minute, e.g., 0.5 liters per minute, 2 liters per minute, 3 liters per minute, 6 liters per minute, 9 liters per minute, or other gas flow rates. The pulse repetition rate (i.e., the pulse consisting of several radio frequency voltage oscillations) can be arbitrarily selected in the range of about 100 - 600 hertz or about 200 - 500 hertz. The pulse can optionally range from about 100 microseconds - 1000 microseconds; e.g., about 400 microseconds, 600 microseconds, or other pulse lengths.

[0152] Optionally ( Figure 1B ), the plasma treatment device 55 includes a secondary fluid supply 63, which can be a source of clean pressurized air, or another gas component, e.g., oxygen and nitrogen in non - atmospheric proportions. The provided gas composition can optionally include other species, such as water vapor, and the fluid can optionally be in liquid form: e.g., saline or water.

[0153] Although the secondary fluid supply 63 can provide a second ionization gas (e.g., an alternative ionization mixture provided by the ionization gas supply 61), the composition provided by the secondary fluid supply 63 itself is not the ionization gas of the plasma treatment device 55, which is a special feature of some embodiments of the present disclosure; that is, its unmixed form is not suitable for ionization through the plasma delivery tip 66 (e.g., its ionization energy is too high). However, the composition may contain substances that are partially ionized or otherwise react in the presence of a plasma. In some embodiments, the substances as these secondary reaction products may be involved in the therapeutic effects caused by plasma exposure. For example, the gas delivered from the secondary fluid supply 63 can be used for the flow of the ionization gas as described; for example, at a flow rate between 0.1 liters per minute and 10 liters per minute. The liquid can be delivered at a lower rate, such as 0.01 liters per minute to 0.1 liters per minute, or at another rate. The gas and liquid deliveries themselves can be alternated. Generally, the secondary fluid supply 63 itself may include multiple fluid supply sources, which can be mixed and / or alternately selected for delivery.

[0154] In a schematic representation, the secondary fluid supply 63 is depicted as a pump, but it can also be provided from another pressurized source (such as a tank). If the fluid is selectively filtered, for example, filtered to remove biological contaminants. The secondary fluid supply 63 itself is optionally provided as part of the plasma treatment device 55; optionally the plasma treatment device is configured to receive (e.g., through the tube 75) the secondary fluid from an externally provided source (such as a compressed air distribution system in a hospital building).

[0155] In some embodiments, the pipeline 72 ( Figure 1A ) is replaced by multiple pipelines 75, 77, 79 ( Figure 1B ). The switching valve 64, in some embodiments, operates to provide alternating gas from the pipeline 79 to the handle 80 from the pipeline 77 (connected to the ionization gas supply 61) or the pipeline 75 (connected to the secondary gas supply 63).

[0156] A potential advantage of this arrangement is that it allows for the periodic injection of molecular substances, and although the initially generated plasma does not require molecular substances (and even does not interfere with the generation of molecular substances), the therapeutic effects can still be adjusted. Here, these substances are referred to as "supplementary substances". In particular, the plasma treatment effects verified under open atmospheric conditions may be altered (even with the same plasma generation parameters) when the plasma is delivered to an enclosed space, such as a body cavity. Even if there is a certain degree of gas initially present, such as nitrogen or oxygen, these gases may be consumed or replaced (e.g., by the ionization gas) as the plasma generation proceeds. This can apply to the molecular substances in the environment as well as to the molecular substances at the treatment target point itself.

[0157] More particularly, alternating between the two sources has the potential advantage of introducing the supplementary material into the lumen space without the need to change the mixture of the ionized gas that serves as the primary medium for plasma generation. For example, the gas from the secondary gas supply 63 can provide the ionized gas for about 20 seconds every 1 - 5 seconds (the duty cycle is between 20:1 and 4:1). In some embodiments, another ratio is used; for example, a ratio of approximately between 5:1 and 60:1, such as 10:1, 30:1, or 60:1. In some embodiments, the duty cycle is approximately between 7:3 (70% ionized gas delivery phase) and 99:1 (99% ionized gas delivery phase). The duty cycle can be set arbitrarily according to another measurement unit (such as volume at atmospheric pressure).

[0158] The potential advantage of using the unmixed ionized gas from the ionized gas supply 61 is that the ionization energy can be kept low. For example, the voltage can be kept within 30% of the threshold voltage that can reliably ionize the unmixed ionized gas. This is a potential advantage, which in turn is for electrical and / or thermal safety, and / or the ability to maintain a small device cross-section (for example, 7 mm diameter or less; the width of the wiring and insulation itself depends on the power and voltage requirements). If the device operates near the breakdown threshold, even if a very small proportion of the supplementary material gas is introduced, there may be no or insufficient reliable ionization. Therefore, it is best to completely stop the delivery of the ionized gas to allow a higher delivery rate of the supplementary material and shorten the interruption time during the time duration of plasma generation.

[0159] In addition, in some embodiments, in order to control the generation of the plasma and / or verify that the plasma is being delivered as planned, the spectral characteristics of the plasma are monitored. Mixing the ionized gas with the supplementary material may complicate the monitoring, for example, by adding spectral lines to confound the monitoring measurements.

[0160] However, in some embodiments, the switching valve 64 can be controlled to optionally allow partial mixing of the gas from the two gas supply sources 61, 63 during the supplementary material delivery phase. This may allow the plasma generation to continue under sub-optimal conditions (for example, higher operating voltage and / or uncertain operating results) rather than being completely interrupted. Another potential use of the partial mixing is to determine (based on the percentage of quenched plasma generation by mixing) how high the breakdown voltage threshold at which the device actually operates is without adjusting the voltage itself.

[0161] In some embodiments, the duty cycle frequency is set such that the plasma delivery phase is longer than 10 seconds, such as 20 seconds, 30 seconds, or other times. The delivery phase of the supplementary material may be selected to be between about 0.5 - 10 seconds. The longer uninterrupted plasma delivery phase in the duty cycle may make it easier to track the location where the plasma is actually delivered, and / or may help maintain the stability of the plasma plume itself. However, if the time is too long, the supplementary material may be depleted. Accordingly, the duty cycle can be adjusted based on the estimated or observed (such as spectroscopically observed) depletion rate of the supplementary material.

[0162] In accordance with some embodiments of the present disclosure, reference is now made to Figure 2A , which is a schematic diagram showing a plasma delivery tip 66, including a pre-chamber 20, which provides a longitudinal separation between a plasma generation site near the discharge electrode 106 and an external volume 11 surrounding the plasma delivery tip 66.

[0163] Figure 2A A general schematic diagram of the plasma delivery tip 66 with the pre-chamber 20 is provided. The circumferential wall 101A defines the pre-chamber 20. The distal end of the pre-chamber 20 opens into the external volume 11, and the proximal end terminates at the plasma generation region 12 of the plasma delivery tip 66, including the circumferential wall 102A and the electrode 106, which together define some important electrical and geometric characteristics that affect the generation of the plasma plume 10. These characteristics include (1) the inner diameter of the circumferential wall 102A, (2) the breakdown voltage of the dielectric barrier separating the electrode 106 from the lumen 95 of the circumferential wall 102A, (3) the proximal-to-distal length of the electrode 106, which affects the output voltage of the plasma. A voltage is provided to the discharge electrode 106 along the electrical conduit 105, which may optionally be a coaxial cable.

[0164] In some embodiments, the circumferential wall 101A surrounds a cavity space (pre-chamber 20) whose diameter is larger than the space enclosed by the circumferential wall 102A. In some embodiments, the distal hole 21 of the circumferential wall 101A is located at a fixed longitudinal distance from the end of the circumferential wall 102A (as long as the circumferential wall 101A remains unfurled), or at a longitudinally adjustable distance within only a short range (e.g., within a range of 50 millimeters or less, 20 millimeters or less, 10 millimeters or less, 5 millimeters or less, 1 millimeter or less). Thus, the longitudinal length of the pre-chamber 20 is fixed or short-range adjustable accordingly. This differentiates the circumferential wall 101A from an overtube where the plasma generation region 12 can be moved forward or backward to any distance. Potential advantages of the fixed-length or near-range adjustable-length pre-chamber 20 include preventing the plasma generation region 12 from crossing the hole 21 (which may expose it more directly to fluid contamination), and maintaining more certainty in the generation of the plasma plume 10 within its range so that it can reach the hole 21 (and optionally a plasma processing target placed there).

[0165] Another potential advantage is that a larger treatment target area can be selected for plasma plume treatment. For example, when the distal hole 21 is pressed against the treatment target, the action of the plasma plume may expand to a larger area than when there is no lumen dilation. At the same time, the geometric parameters of plasma generation (in the plasma generation region 12) are partially decoupled from the diameter of the anterior chamber 20. The thickness ratio of the circumferential wall 101A to the circumferential wall 102A (i.e., within the plasma generation region 12) can be selected as 1:2, 1:3, 1:4 or greater. The wall thickness ratio can be selected in the reverse, for example, 2:1, 3:1, 4:1 or less, which, with a constant outer diameter, results in a narrower outlet and potentially increases the ejection speed 10 of the plasma plume. This may increase the mixing of the plasma plume 10 with the surrounding ambient fluid; this is a potential advantage, for example, in improving fluid activation efficiency.

[0166] The circumferential wall १०१A can be selected as "blunt" or "sharp" (compare, for example, Figure 2B and 2C of the embodiments). The anti-collapse ability of the circumferential wall १०१०A can be selected according to the expected conditions. A more rigid circumferential wall १०१०A has potential uses, for example, as a trocar for penetrating tissue, which can be selected to be made of metal (optionally polymer-coated) or a rigid polymer.

[0167] A more yielding circumferential wall १०१०A is potentially useful, for example, as a non-invasive tip for guiding within delicate body cavities. The circumferential wall 101A can be optionally configured as an elastically deformable membrane with a thickness less than 1000 microns; for example, about 500 microns, about 250 microns, about 100 microns, or other thicknesses. In addition, the circumferential wall 101A is made of a material that is soft and easily elastically deformed at the selected thickness, for example, it will fold when the external pressure is less than about 2 bar, 1 bar, 0.5 bar, 0.25 bar, 0.1 bar, 0.05 bar or other pressures. During plasma delivery, the internal pressure exerted by the flowing discharge gas helps the circumferential wall 101A resist folding, for example, when pressed against the target. The thicker circumferential wall 102A provides support from the proximal side.

[0168] The plasma plume 10 is also affected by the adjustment of the direction and symmetry of the elements in the plasma generation region 12. Figure 2A The structure generally represents Figure 2B-2E arrangement, where plasma is generated using an ionized gas 8 flowing along a lumen 95 defined by a circumferential wall (the wall of the lumen 95 and / or the tube), and circumferentially positioned discharge electrodes 106 extend around the lumen 95, at least partially around the circumference of the lumen 95. It should be understood that a pressure-maintained pre-chamber 20 is optionally provided for other arrangements; for example, an arrangement using discharge electrodes surrounded by an ionized gas flow, as Figure 3A shown (without valves).

[0169] In some embodiments, the plasma delivery tip 66 is configured to deliver plasma to a target in an environment 11 that includes water molecules, water-saturated gas, and / or free liquid, and may even be liquid-immersed. However, contaminants (e.g., aqueous solution contamination) can very quickly inhibit the plasma plume, preventing its effective delivery to the target. Even if the plasma plume is not completely inhibited, the parameters of plasma generation may also change unpredictably due to contaminants.

[0170] In some embodiments, contamination is prevented (i.e., continuously "blowing" out the ionized gas from the distal holes of the delivery tip) by maintaining a constant positive pressure of the ionized gas 8 within the inner cavity of the plasma delivery tip 66, preventing contaminants from entering the pre-chamber 20. For plasma delivery, the distal hole 21 of the pre-chamber 20 is optionally pressed against the target, and / or a lumen space that can clear blocked contaminants is inserted, for example, partially or completely cleared by the gas pressure exerted by the flow of the ionized gas 8. For small cavity devices (e.g., devices with a cavity diameter less than or equal to 5 mm), the amount of gas discharged may be so low when maintaining a positive pressure that the problem of expansion can be ignored; if not, some of the blown-out gas is optionally cleared by a return cavity.

[0171] It should be noted that this method of preventing liquid from flowing back into the pre-chamber 20 and / or the plasma generation region 12 has a potential drawback, namely, generating a continuous gas flow within the body cavity where the plasma delivery tip 66 moves, which may not always be acceptable. For example, gas clearance from the cavity of the plasma delivery tip 66 may not always be available to control pressure buildup. There may also be a risk of liquid contamination if the back pressure exceeds the forward pressure of the gas, for example, if the plasma delivery tip enters a particularly narrow space. In addition, it is possible to freely and completely shut off the ionized gas flow according to a command, which is a potential advantage, for example, eliminating interference (e.g., bubbling) caused by the continuous gas flow, which may interfere with imaging and / or process monitoring.

[0172] According to some embodiments of the present disclosure, reference is now made to Figure 2B -2E, a schematic diagram showing a valved configuration of a plasma delivery tip that generates plasma using an ionized gas 8 flowing along a lumen extending around circumferentially positioned discharge electrodes 106. Figures 2B - 2CShows the closed (left panel) and open (right panel) configurations of the same corresponding embodiment.

[0173] In Figures 2B - 2C , the walls of the prechamber 20 are represented by the circumferential wall 101. In FIG. 2D, the prechamber 20 is defined within the circumferential wall 101A, different from the scavenging lumen 96. In FIG. 2E, the prechamber 20 is defined by the circumferential wall 101 (e.g., if extending beyond the circumferential wall 101B) or by the circumferential wall 101B. Corresponding to Figure 2A in the plasma generation region 12, the components are a cross-sectional view of the electrode 106, as a coil, a dielectric barrier layer 103 (determining the breakdown voltage), another insulating layer 102 (providing mechanical support and / or electrical insulation from the outside to the electrical conduit 105), and the electrode 106. Optionally, these different layers are assembled together by different components (e.g., different materials), or formed integrally (e.g., as Figure 2A shown). The different layers can be fixedly connected to each other or movable (e.g., longitudinally slidable and / or rotatable).

[0174] In Figure 2B , a check valve 110A is located within the prechamber 20. When there is no ionized gas 8 flowing in the gas delivery chamber 95, the valve 110A remains closed. During plasma generation, the valve 110A opens, allowing the plasma plume 10 to project forward.

[0175] The valve 110A is more specifically shown in the figure as a single-leaf valve 110A, but it should be understood that other valve designs can be alternatively used; for example, the valve designs described herein. A common feature of many such valve designs is that when they open, they leave a sufficiently clear small hole for the plasma plume 10. However, the valve can also be used to restrict and / or redirect the plasma plume, such as Figure 3F discussed in. Optionally, the position of the valve 110A is such that it remains entirely within the prechamber 20 when open. This allows the hole 21 to be fully pushed towards the target without valve interference.

[0176] Optionally, the valve 110A is driven to open by the pressure of the ionized gas 8 delivered from the proximal end of the valve 110A. As a check valve, pressure from the distal end does not open the valve 110A, making it a barrier to the entry of liquid. Additionally, the valve 110A can be driven independently of the gas pressure, such as the valve 110D ( Figure 3E) Optionally, side vent holes 113 are provided in the wall of the front chamber 20, allowing the ionized gas to escape even if the distal hole 21 is blocked (e.g., by pressing against the tissue to be treated). In some embodiments, this can prevent the accumulation of backpressure when the valve 110A is closed or partially closed. Additionally, or as an alternative to the holes 113, the distal circumference of the distal hole can be configured with notches that provide a path for the gas to escape. This also potentially provides an advantage of maintaining a more constant pressure near the electrode 106, e.g., avoiding cycles of pressure buildup and release due to the occurrence and overcoming of temporary blockages.

[0177] In Figure 2C , the front chamber 20 is formed by the trocar tip (i.e., the beveled needle tip, defined by the beveled distal hole 104). Optionally, the beveled needle tip helps to penetrate obstacles, e.g., membranes or narrow channels. In most configurations, the beveled needle tip may also provide a natural vent for the ionized gas. It may retain the gas for a sufficient length of time (especially if embedded in soft tissue) such that the liquid can be kept away from the plasma plume until it reaches the target tissue surface for treatment.

[0178] In some embodiments, the ionized gas is allowed to dissipate (e.g., through natural or artificial body orifices). Optionally, the ionized gas is actively cleared, e.g., through channels separate from the probe catheter 73, and / or through channels integrated into the probe catheter 73.

[0179] Figures 2D - 2E respectively add a gas scavenging lumen 96, 97 to the general configuration of Figure 2B , allowing the return flow 9 of ionized gas and / or liquid. In Figure 2D, the scavenging lumen 96 is a separate lumen that runs parallel to the lumen 95. In Figure 2E, Figure 2B the entire device portion of

[0180] is partially filled with the circumferential wall 101B, and the gas returns along the unoccupied internal volume of the circumferential wall 101B. Figure 2B Notably, in the illustrated configuration of the embodiment of Figure 2E, the circumferential wall 101B effectively defines the distal diameter of the front chamber 20, and the scavenging of the gas can occur without the gas having to leave the front chamber 20. Optionally, the circumferential wall 101 extends beyond the supertube 101B; then the front chamber 20 as shown in

[0181] In some embodiments, the circumferential wall 101B includes a tube through which (e.g., the wall of a working channel or conduit) the circumferential wall 101 advances longitudinally along its free end. In some embodiments, the circumferential wall 101B is positioned in a longitudinal relationship with the circumferential wall 101 that is fixed or has limited adjustment (e.g., adjustable up to 5 mm or 10 mm). Optionally, the circumferential wall 101 may move freely radially within the circumferential wall 101B. Optionally, the circumferential wall 101 is fixed to a fixed or adjustable radial position, e.g., by a spacer.

[0182] Now referring to Figures 3A - 3F , Figures 3A - 3F The schematic shows the valve structure of a plasma delivery tip. According to some embodiments of the present disclosure, the plasma delivery tip generates plasma using an ionized gas 8 that flows through the lumen where the discharge electrode 306 is located. Figures 3A - 3B The closed (left panel) and open (right panel) configurations of the same respective embodiments are shown.

[0183] Figures 3A - 3D Typically corresponding to Figure 2B -2E embodiments, the only exception being that the plasma generation region 12 is now achieved by the flowing ionized gas 8 around the discharge electrode 306 located within the lumen 96 and is insulated from the ionized gas 8 by the surrounding dielectric barrier layer 303.

[0184] Figure 3B Illustrates a slit valve 110B (also one-way), which is optionally provided to any embodiment, e.g., Figures 2A - 3D the vane valve 110A in

[0185] Figure 3E Shows a longitudinally expanding valve 110D, optionally implemented as a piezoelectric one-way valve. Although it is not primarily pressure-driven, the valve 110D may be selectively opened only when the proximal gas pressure increases (to prevent fluid entry). For example, the valve 110D is opened under the control of a controller 55, which also controls the delivery of the ionized gas. The electrical conduit 311 delivers voltage to a valve component composed of a piezoelectric material layer 331 and a conductor layer 330. The differential bending caused by the applied electric field causes the valve 110D to open (assuming the valve is normally closed; the drive for opening / closing may have different optional configurations, e.g., reversed). If an optional valve structure is used, e.g., Figures 2B - 3D in conjunction with any valve embodiment in

[0186] Figure 3F (similar in other respects to Figure 3B ) has a one-way flap valve 110E (or another asymmetric opening valve design). Optionally, the asymmetry of the opening of the valve 110E is used to affect the directionality of the plasma plume 10. Figure 3FThe three panes (left, middle, right) show three different valve opening states (closed, half-open, almost fully open). Optionally, the degree of valve opening is controlled by the pressure of the flow of the ionized gas 8. The flap of the valve 110E may quench the plasma reaching it. One way to mitigate this is to provide the flap of the valve 110E with a charge that easily deflects the plasma.

[0187] Again, it should be understood that the valve designs described herein are merely examples and there is no particular limitation to specific embodiments that use only the valve configurations shown.

[0188] Now referring to Figures 4A - 4C , according to some embodiments of the present disclosure, Figures 4A - 4C A distal view schematically showing different valve designs. Figure 4A Corresponding to the distal view of the flap valve 110E (i.e., Figure 3F The valve 110E shown from the side in Figure 4B Corresponding to the distal view of the slit valve 110B (i.e., the valve 110B shown from one side of Figure 3B ) Figure 4B Corresponding to the distal view of the vane valve 110A (i.e., the valve 110A shown from the side looking inwards, e.g., Figure 3A )

[0189] Now referring to Figures 5A - 5B , Figures 5A - 5B Schematic diagrams showing views of the expandable tip plasma delivery tip 501 in the folded ( Figure 5A ) and expanded ( Figure 5B ) configurations, respectively, according to some embodiments of the present disclosure. The left panel shows a sectional view and the right panel shows an external view. Also referring to Figure 5C , according to some embodiments of the present disclosure, Figure 5C Schematically shows a sectional view of the expandable tip plasma delivery tip 504 in the folded and expanded configurations. The left panel shows a folded view; the right panel shows an expanded view. The plasma delivery tips 501, 504 illustrate structural variations of some features of the expandable plasma delivery tips.

[0190] In some embodiments, the plasma delivery tips 501, 504 include a plasma generation region 12 configured to generate plasma from the ionized gas 8 flowing through an enclosed cavity extending from discharge electrodes positioned circumferentially, e.g., as described in relation to Figure 2B -2E in this example. The plasma generation region 12 is enclosed within an expandable sheath 502. When folded ( Figure 5A) When expanded, the expandable sheath 502 is substantially sealed to prevent liquid from entering through its distal end 503. During expansion, the distal end 503 of the expandable sheath 502 expands to form an anterior chamber 20, which optionally has a distal outer diameter that is 1.5 times, 2 times, or greater than the proximal outer diameter of the expandable sheath 502. This potentially allows the plasma plume 10 to be delivered simultaneously to a correspondingly larger area of the target surface 30. The expandable plasma delivery tips 501, 504 also provide a potential advantage against clogging (e.g., during device advancement), as the anterior chamber 20 remains completely closed from the external environment until the distal end 503 expands and / or pressure from the ionized gas 8 is applied. It should be noted that the treatment area can be optionally reduced by further pressing the distal tips 501, 504 until the anterior chamber 20 formed by the distal end 503 is substantially excluded from the plasma flow (and may be folded or even everted), while the plasma generation area 12 itself contacts or almost contacts the target surface 30. This potentially provides the expandable plasma delivery tip with an optional variable treatment area capability.

[0191] In some embodiments, the distal end 503 is normally closed; for example, it is elastic and / or magnetic and prone to folding. In some embodiments, the distal end 503 includes elastic (e.g., nitinol, fiberglass, or polymer) struts connected by a thin fabric, or an elastic material (e.g., rubber), whose shape makes it prone to shrink to a folded configuration. In some embodiments, the conversion from the folded tip to the expanded tip is driven by the pressure from the flow of the ionized gas 8. Optionally or additionally, the conversion is driven by another method; for example, piezoelectric activation bending and / or mechanical drive (e.g., by pulling, pushing, or rotating a control member).

[0192] In some embodiments, the reaming drive of the distal end 503 utilizes thermally driven shape memory properties. For example, the device can be elastically configured to be closed at body temperature and elastically configured to be opened at a lower (preferably) or higher temperature. Optionally, the distal end 503 is configured to use a material that is prone to elastic deformation in the opposite configuration - either towards folding or towards expansion. At body temperature or higher, the balance of forces between the two causes collapse. Nitinol shape memory alloy is prone to softening (and losing elasticity) below its critical temperature. In some embodiments, at least some of the collapsible struts are formed by allowing nickel-titanium alloy, allowing softening between body temperature and cold plasma temperature (e.g., between about 37°C and about 25°C). After softening, the balance of forces changes, causing the distal end 503 to expand. This can be optionally achieved using struts of two different nitinol alloys (i.e., with different transition temperatures), where the struts of the nitinol alloy act on the rubber polymer that is prone to assume an expanded shape, or other structures.

[0193] When the distal end 503 is pressed against the target surface 30, the target surface 30 provides closure of the orifice of the anterior chamber 20, helping to maintain sufficient internal pressure for inflation. At least at this pressure, the ionized gas 8 escapes from around the distal edge of the expanded distal end 503 and / or is evacuated through one or more gas evacuation lumens 596 (e.g., the plasma delivery tip 501 as shown in the figure)( Figures 5A - 5B ). Potentially, the evacuation gas actively helps to maintain the consistency of the "expanded" state of the expanded distal end 503.

[0194] In some embodiments, the distal end 503 is self-expanding if not held closed, for example, by an adhesive and / or by another structure. Evacuation through the gas evacuation lumen 596 can be carried out in the case of active suction. This potentially prevents leakage of gas around the distal edge of the expanded distal end 503. Optionally, suction helps to evacuate the liquid in the volume surrounded by the expanded distal end 503. In some embodiments, the evacuated volume is created in a surrounding liquid-filled environment (e.g., a heart chamber), for example, by using suction on the target surface 30 to create an isolation chamber and evacuating the liquid from the chamber, thereby allowing the application of plasma treatment.

[0195] Brief reference Figure 5D to, in some embodiments according to the present disclosure, Figure 5D is a cross-sectional view schematically showing the expandable tip plasma delivery tip 505 in folded and expanded configurations. The plasma delivery tip 505 employs a configuration of a dielectric barrier layer 303 and a plasma discharge electrode 306, which are located in the flow of the ionized gas 8. This alternative configuration of the plasma generating tip device is for the same function as the expandable sheath 502 and the distal end 503 described in Figures 5A - 5C (or Figure 5E ).

[0196] The tip seal of the expanded distal end 503 in its closed configuration can optionally be achieved by maintaining its sufficient closure (e.g., due to its pre-elastic arrangement) such that any residual orifice at the tip is resistant to moisture, for example, due to it being potentially immersed in the surface tension of a liquid. The material of the tip can optionally be generally hydrophobic or treated with a hydrophobic coating. The tip can be configured with a thinned and / or folded webbing material to obtain a sharper tip (e.g., as shown in Figure 5A ), or a blunter tip ( Figure 5C ). Optionally, a secondary seal is provided within the expanded distal end 503, for example, when the distal end 503 is folded, the short leaves meet and are pulled out when the distal end 503 expands. Optionally, a secondary seal is provided outside the expanded distal end; for example, in the form of a "calyx", as described in Figure 5E .

[0197] Optionally, the distal end 503 is initially closed by a connection that breaks upon dilation (e.g., an adhesive bond and / or a thin bridge of interconnecting material). It should be noted that relying on a one-time closing mechanism may interfere with redeployment after the device is withdrawn, but this may be acceptable in certain applications (e.g., single-use, single-target applications). Optionally, configure the distal end 503 (e.g., by using an internal surface coating) to be self-adhesive. After dilation, the distal end 503 can be reset to the folded configuration by retracting it into the closure cavity, causing the surfaces of the distal end 503 to adhere to each other, restoring the closed and self-sealing structure.

[0198] Now referring Figure 5E , in accordance with some embodiments of the present disclosure, Figure 5E The schematic diagram shows, in cross-section, an expandable tip plasma delivery tip 506 having folded and expanded configurations and including a calyx 510.

[0199] The expandable plasma delivery tip 506 is generally configured similarly to Figures 5A - 5D one of the expandable plasma delivery tips in

[0200] and includes the calyx 510. For example, the calyx 510 is optionally provided to enhance sealing and / or to provide a thinner and / or sharper point at the distal end 503 when in its folded configuration. It is noted that a more conical configuration provides a potential advantage in using the plasma delivery tip 66 to guide through narrow body cavities; and / or penetrate, for example, solid tissue, body cavity walls, and / or tissue membranes. Due to the effects of surface tension, using a sharper angle and / or a smaller aperture also helps to exclude liquids.

[0201] The calyx 510 is composed of one or more vanes 510A (or, using a botanical analogy, "sepals" 510A) attached to the outer proximal end of the plasma delivery tip 506. Their shape is such that they close the distal end of the plasma delivery tip when folded and split (without a completely circumferential web connection) when the distal end 503 expands. Optionally, the calyx 510 tapers to a thin upper end. Optionally, the vanes 510A are configured to connect and / or overlap (and / or with themselves) when folded. Optionally, the vanes 510A are themselves interconnected by a membrane along at least a portion of their length, potentially enhancing their ability to provide a contamination-free seal.

[0202] Optionally, the calyx 510 is formed mainly of a soft and flexible material, e.g., to provide an atraumatic tip. In some embodiments, the calyx 510 is more like a thorn or a needle; e.g., including metal and / or hard plastic parts (optionally sharpened). This may assist in tissue penetration and / or manipulation; e.g., penetrating to reach a plasma treatment target, and / or preparing (e.g., in-situ dissection and / or making more permeable) the plasma treatment target.

[0203] Notably, the calyx 510 can be considered an “outer valve” that can be opened, e.g., by internal pressure; yet still protects (when it is closed) against contaminants entering. Optionally, the calyx 510 is provided for sealing the distal end of the non-dilated pre-chamber 20, e.g., Figures 2A - 3F the distal end of one of the embodiments (in Figures 2B - 3F which case, optionally, an internal valve is retained or omitted). When closed, the calyx 510 serves to prevent contaminants from entering, but when opened, it does not define the pre-chamber 20; rather, it peels into unconnected parts, revealing the pre-chamber 20 located below and / or proximally.

[0204] According to some embodiments of the present disclosure, now referring to Figure 5F , Figure 5F the schematic illustration depicts the deployment of the self-expanding distal end 506 from the introducer 515. The distal end 506 (e.g., for plasma delivery, as described in relation to the distal end 503) is prone to elastic expansion but is kept closed by the introducer 515, e.g., folded within the lumen of the introducer 515. Panel 521 shows the distal end 506 fully covered by the introducer 515. Panels 522, 523 show the distal end 506 expanding as it is un-sheathed, and panel 524 shows the distal end 506 fully un-sheathed and in contact with the target surface 30, with ionized gas flow (arrow heads pointing away from the surface 30) escaping under pressure.

[0205] Plasma treatment methods and scenarios

[0206] Now referring to Figures 6A - 6C , according to some embodiments of the present disclosure, Figures 6A - 6C schematically represents an access mode according to some embodiments of the present disclosure that allows for plasma to be provided to a plasma treatment target 1603 located within the lung 20. Further referring to Figure 6D , according to some embodiments of the present disclosure, Figure 6D provides a detailed view corresponding to an example of the plasma delivery configuration for Figure 6C . Also referring to Figure 6E , according to some embodiments of the present disclosure, Figure 6E is a schematic flow chart of a method for performing plasma treatment within a body cavity.

[0207] In Figure 6AIn [reference], the probe catheter 73 passes through the trachea and bronchi 24 of the lung 20 and is advanced forward (e.g., under image guidance) until it is positioned within the range of the target 603, generating a plasma plume 10 from the target 603.

[0208] In Figure 6B [reference], the probe catheter 73 has been introduced percutaneously (through the body wall 22) via an introducer 605 to a position within the range of the target 603, from where the plasma plume 10 is generated.

[0209] In Figure 6C [reference], the first probe 73A has passed through the trachea and bronchi 24 of the lung 20 and is advanced forward (e.g., under image guidance) until it is positioned within the range of the target 603. The second probe 73B has been introduced percutaneously (through the body wall 22) via an introducer 605 to a position within the range of the target 603. Operating simultaneously, the probes 73A, 73B generate the plasma plume 10. Any one of the probes 73A, 73B can be a voltage source, any one can be a provider of ionized gas and / or a fluid containing a supplementary substance, and any one can provide an evacuation chamber for exhausting the provided fluid. Probes 73F, 73G show different probe placement positions. Probe 73G includes a trocar in this example, and probe 73F is a pointed probe that enters the lung parenchyma from the trachea / bronchial passage. Optionally, blood vessels (especially veins) are used for such a hybrid path. The probe is brought to the general vicinity of the target tissue through a blood vessel of sufficient diameter and then deviated through the vessel wall to reach the target itself. The positioning of any one or more probes can be done under manual control and / or using a robotic positioning system.

[0210] Figure 6D More details show how to configure Figure 6C an example of the scenario. In the example shown, the probe 73A is a capped plasma delivery tip (optionally, as Figure 5D shown), introduced through the trachea and bronchi and coinciding with the target surface 30, which will be treated by exposure to the plasma. In this example, the probe 73A provides voltage through a discharge electrode assembly 306. Alternatively, a circumferential electrode around the cavity is provided as the discharge electrode. The trocar 73B has been introduced percutaneously through the surface 30 into the hood of the probe 73A, from where it can perform one or both functions of delivering a fluid (such as ionized gas) and exhausting the fluid. When the ionized gas flows through the discharge electrode assembly 306, the plasma 10 is generated and redistributed according to the gas flow, which may fill the entire hood area. The cavity of the probe 73A can be used to exhaust the gas provided by the probe 73B or to provide the gas exhausted by the probe 73B. Suction can be used to create a slight negative pressure, which has the potential advantage of preventing gas leakage into the surrounding environment of the probes 73A, 73B and can also optionally remove potential contaminants from the plasma working volume.

[0211] Alternatively, the gas can also be discharged around the edge of the hood as Figure 5D described. Optionally, the cavities of the probes 73A and 73 are used to provide a fluid input to the treatment area; for example, one of the probes provides an ionized gas and the other provides a fluid composed of supplementary substances (such as nitrogen, oxygen, and / or water molecules).

[0212] Referring to Figures 6A - 6B the method in the context of Figure 6E : Corresponding to block 610, in some embodiments, the target is located, for example, using MRI imaging, CAT imaging, PET imaging, or other methods.

[0213] Corresponding to block 612, in some embodiments, the plasma delivery tip 66 is guided through a percutaneous incision through the introducer 605 to the area of the target 603( Figure 6B ), or through a catheter system or as its own guiding device( Figure 6A ). The plasma delivery tip 66 can optionally provide a sharp tip (such as a trocar or a pointed tip) or a non-invasive tip. The probe catheter 73 equipped with the plasma delivery tip 66 can optionally be guided, optionally provide a working channel for receiving a wire (or other tool), and / or optionally be inserted through the working channel of a catheter device or an endoscope.

[0214] Describing embodiments of the trocar tip, for example, related to Figure 2C , 3B or 3F; for example, for Figures 5A - 5E pointed or non-invasive expandable embodiments are described. Optionally, a blunt-tip plasma delivery tip 66 is used. The arrangement of the target area 603 can be selected from the arrangements related to the target area 703.

[0215] Corresponding to block 614, in some embodiments, the use of an auxiliary evacuation lumen is optional. In some embodiments, evacuation is not required (for example, the gas escapes through the bronchi and trachea). Optionally, the probe catheter 73 itself has one or more gas evacuation lumens. If used, the auxiliary evacuation lumen can be introduced by any suitable method. Optionally, the distal end of a standard catheter system is introduced near the target 603 and used for passive evacuation of the ionized gas (due to the pressure in the treatment seat forcing the gas through it) and / or negative pressure.

[0216] Corresponding to block 616, in some embodiments, the area of the target 603 is treated with plasma. Whether there is a problem with liquid drainage depends on the condition of the lungs and the location of the target 603. FIG. 7 describes several examples of how the plasma delivery tip 66 is moved during the treatment, which are also applicable to Figures 6A - 6B the available options in the examples of

[0217] Now refer to Figures 7A - 7C , according to some embodiments of the present disclosure, Figures 7A - 7C schematically shows the application of plasma therapy to a target 703 in a solid organ 704. In Figure 7A , the probe 73 is inserted into the target 703 region within the solid organ 74 (e.g., the liver). In Figure 7A 's example, the plasma delivery tip 66 includes an expandable distal end. In Figure 7B , one or more probes 73C are introduced from different angles (simultaneously or at different times) to allow treatment of different regions of the target 703. In Figure 7C , the plasma is generated using the probe 73D, which includes a discharge electrode assembly 306 and is positioned in the ionization gas provided by the second probe 73E. Using multiple probes, the functions of ionization gas delivery, power delivery (ionization), and ionization gas ventilation can be arbitrarily performed by any given probe in any given combination; for example: gas delivery and gas ventilation, gas delivery and ionization, and / or gas ventilation and ionization (with the remaining functions being handled by at least one of the other multiple probes). These three functions can optionally be divided among three probes, with each probe handling one of the functions. The functions can also be replicated; for example, multiple probes performing any of the functions of gas delivery and gas ventilation, gas delivery and ionization, and / or gas ventilation and ionization. Optionally, the probe can be combined with any of the other three functions just named or can separately provide supplementary substances.

[0218] Optionally, for targets on the outer surface of the solid organ and / or on the surface between the leaves of the solid organ. The target points include, for example, tumor regions or pathogenic infection regions (such as bacteria, viruses, and / or fungi).

[0219] In Figures 7A - 7C 's context, refer to Figure 6E 's method: Corresponding to block 610, locate the target, for example, using MRI imaging, CAT imaging, PET imaging, or other methods.

[0220] Corresponding to block 612, the plasma delivery tip 66 and / or other probes 73C - 73E are guided to the target region through a percutaneous incision by the introducer 705. If necessary, standard devices such as needles and / or trocars can be used to penetrate the organ itself. Optionally, use the tip embodiments of the plasma delivery tip 66; for example, the trocar tip embodiments, such as according to Figure 2C , 3B or as described in 3F; or the expandable tip embodiments, for example, having a sharp and rigid calyx 510 as in Figure 5EVersion of the embodiment. Optionally, the target 703 is prepared for plasma treatment by incision or other partial stripping, which may increase the surface area directly exposed to the plasma; and / or loosen the treatment area to allow for greater expansion of the plasma delivery tip.

[0221] Corresponding to block 614: For intraperitoneal surgery (usually inflated), a separate gas scavenging lumen is optionally omitted. However, for a deeply buried target 703, there may be a tendency for the ionized gas to expand and / or disrupt the stability of the working area. For this or other reasons, a gas scavenging lumen may be inserted where it will recover the ionized gas used to generate the plasma.

[0222] Corresponding to block 616: Plasma is actually generated and delivered. This delivery can be accompanied by and / or occur after the plasma delivery tip 66 has expanded (to the extent allowed by the space constraints). Optionally, plasma delivery is accomplished by pressing a portion of the target 703 with the tip 66, using the forechamber 20 to create a liquid-free zone. Optionally, the tip 66 is inserted into a "pocket" from which the liquid flows out (e.g., by the ionized gas), allowing the plasma to be delivered from a position a few millimeters away from the tissue surface. As the plasma delivery tip 66 is gradually inserted into the target body (i.e., inserted, inflated, manipulated, folded, inserted slightly deeper, and repeated), the plasma can be selectively activated multiple times along a trajectory through the target 703. Additionally, or alternatively, plasma delivery is performed during the removal of the plasma delivery tip. A sufficiently large target 703 is optionally treated with plasma in multiple channels, e.g., along multiple insertion tracks through the target area. Optionally or alternatively, a treatment surface is applied to the surface of the target area and / or covers the surface of a shallowly placed target area, allowing the plasma delivery tip 66 to scan the surface.

[0223] Now referring to FIGS. 8A - 8B, according to some embodiments of the present disclosure, FIGS. 8A - 8B schematically illustrate the application of plasma treatment to a target in the urinary tract. FIG. 8A shows the treatment using a rigid cystoscope 810 inserted along the urethra 805, while FIG. 8B shows the treatment using a flexible cystoscope 901 inserted along the urethra 805.

[0224] Now referring in the context of FIGS. 8A - 8B Figure 6E to the method: Corresponding to block 610, the target is located, e.g., using a cystoscope for endoscopy.

[0225] Corresponding to block 612, in some embodiments, the plasma delivery tip 66 is guided through the urethra via a cystoscope 810, 901 to the target area. The plasma delivery tip 66 may be blunt-tipped or provide a tapered non-invasive tip. In some embodiments, the treatment targets 803, 803b are located on the inner wall of the bladder 801, where they are directly exposed to the plasma plume 10 generated by the plasma delivery tip 66. Optionally (position 901B), the flexible cystoscope 901 is directed to the bladder entrance of the ureter 802; from there, the plasma delivery tip 66 is guided to the target 803C deep within the urinary tract.

[0226] Corresponding to block 614, in some embodiments, the use of an auxiliary evacuation lumen is optional. If used, the auxiliary evacuation lumen can be introduced by any suitable method. Optionally, gas evacuation is performed through a separate channel of the cystoscope 805, 901, which is also used to introduce the plasma delivery tip 66. Optionally, a dedicated gas evacuation device is introduced, e.g., through another working channel of the cystoscope 805, 901. Optionally, the plasma delivery tip 66 itself provides one or more gas evacuation lumens.

[0227] Corresponding to block 616, in some embodiments, the target 803, 803B, 803C is treated with plasma. To prevent contamination by residual liquid, even if the bladder 801 itself is substantially empty, a liquid evacuation capability within the plasma delivery tip 66 is desirable. Liquid may also be encountered within the ureter 802 and should be evacuated. FIG. 7 depicts several examples of how the plasma delivery tip 66 is moved during treatment, which also applies to the available options in the examples of FIGS. 8A-8B.

[0228] Now referring Figure 9 , according to some embodiments of the present disclosure, Figure 9 is a schematic flow chart of a method for delivering plasma to a target within a body cavity.

[0229] At block 910, in some embodiments, the distal end of the plasma delivery tip is pressed against the target selected for plasma treatment.

[0230] At block 912, in some embodiments, the distal portion of the plasma delivery tip is expanded; optionally by applying pressure to the ionized gas provided to the plasma delivery tip to expand the plasma delivery tip.

[0231] At block 914, in some embodiments, plasma is delivered.

[0232] Now referring Figure 10 , according to some embodiments of the present disclosure, Figure 10 is a schematic flow chart of a method for delivering plasma to a target within a body cavity.

[0233] In block 1010, in some embodiments, the distal end of the plasma delivery tip is pressed against a target selected for plasma treatment.

[0234] In block 1012, in some embodiments, a valve of the plasma delivery tip is opened. The valve is configured to at least protect plasma generating elements of the plasma delivery tip (e.g., the luminal surface of a discharge electrode along the plasma delivery tip) from contamination.

[0235] In block 1014, in some embodiments, plasma is delivered.

[0236] Now refer Figure 11 , according to some embodiments of the present disclosure, Figure 11 is a schematic flow chart of a method for delivering a plasma-activated fluid to a target surface within a body cavity.

[0237] In block 1102, in some embodiments, the plasma plume is directed onto ambient fluid within the body cavity. Optionally, the ambient fluid includes an aqueous liquid. Optionally, the ambient fluid includes a film of aqueous liquid located between the target surface and a gaseous fluid layer (e.g., having a thickness of about 1 millimeter or less). In some embodiments, the movement of the liquid of the film relative to the surface is governed by surface-to-surface interactions such as surface tension, cohesion, van der Waals forces, and / or Plateau-Rayleigh instabilities. Optionally, the aqueous liquid film includes a layer of water covering the surface of the bladder or stomach and / or another organ of the gastrointestinal tract or urethra. The surface can be the luminal surface of an organ, the outer surface of an organ (e.g., the surface of an abdominal organ accessed laparoscopically), and / or a tissue surface created by dissection, incision, injection, or other surgical procedures.

[0238] Optionally, the ambient fluid includes an aqueous fluid of a greater thickness covering the target surface; e.g., having a thickness greater than 1 millimeter and / or a thickness large enough such that the fluid flows primarily under a pressure (such as gravity) that is independent of interactions with the surface.

[0239] Optionally, the ambient liquid includes a pre-existing and / or naturally occurring body fluid and / or gas. Optionally, the ambient fluid includes a liquid and / or gas artificially introduced into the target surface area, e.g., through an introduced delivery lumen. Optionally, the delivery lumen is part of a plasma generating device that generates the plasma plume.

[0240] In block 1104, in some embodiments, the activated fluid is redistributed over the target surface. In some embodiments, one or more of the following operations performed at block 1104 and / or prior thereto redistribute the fluid:

[0241] · Provide additional fluid near the fluid activation point to force the activated fluid to flow outwards from the fluid activation point. The fluid is optionally provided using the lumen of the plasma delivery device (optionally a gas delivery lumen for delivering an ionized gas), an auxiliary lumen of the plasma delivery device, and / or the lumen of another device. The activating fluid and the fluid for redistribution can be optionally the same or different in composition. In some embodiments, additional liquid is provided over a period of minutes (e.g., 10 minutes) to several hours or days (e.g., a week or longer).

[0242] · The areas around the fluid activation site have been dried beforehand to make them more receptive (e.g., “spongelike”) to the activating fluid diffusing from the fluid activation site. Optionally, the drying is accomplished by using gas from the gas delivery lumen, which can also deliver the gas for generating plasma, an auxiliary lumen of the plasma delivery device, and / or the lumen of another device.

[0243] · Agitate the activating fluid, e.g., direct a gas and / or liquid jet towards the area of the activating fluid. Optionally, the jet is provided by the gas delivery lumen, which also delivers the gas for generating plasma (and may include the plasma plume itself). Optionally, agitation is performed using an auxiliary lumen of the plasma delivery device and / or the lumen of another device.

[0244] Now refer to Figure 12 , Figure 12 which is a schematic flow chart of a method for delivering a plasma-activated fluid to an inaccessible target surface within a body cavity according to some embodiments of the present disclosure.

[0245] In block 1202, in some embodiments, the selected target surface cannot be directly impacted by the plasma plume from the plasma treatment device.

[0246] In block 1204, in some embodiments, the plasma is directed from the plasma treatment device onto a portion of the fluid (optionally, an aqueous fluid) in contact with the target surface. In some embodiments, the fluid includes normal saline. In some embodiments, the fluid includes an inert gas.

[0247] In block 1206, in some embodiments, the activating fluid is redistributed to reach the target surface. For example, one of the operations associated with Figure 11 block 1104 can be optionally selected to actively redistribute the activated fluid.

[0248] In the treatment of some lung diseases (e.g., severe pneumonia cases), the patient's lungs are flushed with normal saline, e.g., to help clear mucus. Optionally, a plasma delivery tip within the lung is used to generate plasma directly on the normal saline. Optionally, the outlet hole of the plasma delivery tip is intentionally immersed in the saline and operated within the saline.

[0249] In the treatment of some lung diseases, the lungs of a patient are treated with alveolar occlusion (such as severe pneumonia) by inflating them with oxygen-containing helium (such as to avoid introducing pressurized nitrogen). In some embodiments, plasma is generated in the oxygen-containing helium mixture. Thus, the helium mixture serves as the ambient fluid and becomes the activation fluid, allowing the distribution of reactive species induced by the plasma into the activation fluid.

[0250] In some embodiments, the activation liquid in the body includes an amount, for example, at least 100 milliliters, 500 milliliters, or 1000 milliliters. The amount of the liquid can be optionally flushed and / or updated; for example, by maintaining the replenishment of the liquid, and / or periodically. The activation of the fluid can be optionally continuous, such as for several minutes (such as 10 minutes), several hours (such as 10 hours), or several days. Through continuous activation, the treatment goal of long-term exposure to plasma-induced reactive substances can be achieved. Optionally, once the plasma delivery device is positioned, it can be operated without the need for active guidance or other direct supervision. Optionally, the plasma delivery tip of the plasma delivery device is placed at a convenient in-vivo location in fluid communication with the treatment target, but not inserted too deep into the body cavity to prevent staying for a long time without continuous direct supervision.

[0251] The distance between the plasma delivery tip and the surface of the target to be treated is optionally separated by several centimeters by the active liquid, for example, at least 3 centimeters, 4 centimeters, 5 centimeters, 10 centimeters, or other distances.

[0252] For example, in some embodiments, the bladder or other hollow organs are treated by keeping them filled with several milliliters of liquid (for example, at least 50 milliliters of liquid), in which reactive substances are continuously induced by the operation of the plasma delivery tip of the plasma treatment device.

[0253] Plasma treatment in a liquid-filled cavity

[0254] Now referring to Figures 13A - 13B , according to some embodiments of the present disclosure, Figures 13A - 13B The schematic diagram shows plasma delivery tips 1301, 1351, which operate to deliver plasma within the lumen space, and a target 1323 within the lumen space 1310 established by the expansion of balloons 1303A - 1303D. Also referring to Figure 13C , according to some embodiments of the present disclosure, Figure 13C is a schematic flowchart of a method using Figures 13A - 13B the plasma delivery tips 1301, 1351.

[0255] In block 1371 ( Figure 13C), where one of the plasma delivery tips 1301, 1351 is inserted into the body lumen wall 1321, which may be, for example, the lumen wall of a blood vessel, the intestine (e.g., the colon), or the lumen of the urinary tract.

[0256] In block 1372, in some embodiments, the balloons 1303A - 1303B, 1303C - 1303D are inflated to seal the lumen space 1310.

[0257] In Figure 13A the example of, balloon 1303A is an annular balloon that is delivered around the cylinder 1302 of the probe tip 1301 and inflated once in place to form a seal with the lumen wall 1321. The distal end of balloon 1303B is inflated to the distal end of the plasma delivery tip 1301, optionally using a separate device or (as shown) by advancing the distal end of the inflation member 1305 to carry balloon 1303B out of the storage chamber 1307.

[0258] Figure 13B The balloons 1303C - 1303D in

[0259] are also annular balloons, each placed on the cylinder 1349 of the plasma delivery tip 1351. The cylinder 1349 also includes one or more holes 1341, 1342 through which fluid passes in and out of the lumen space 1310, as well as fluid conduits 1352, .....

[0260] Emptying may optionally include a flushing phase (using a liquid such as water and / or saline), followed by a purging phase using a gas. Optionally, a drying gas is used to assist in removing residual moisture.

[0261] Once the lumen space 1310 is sufficiently cleared: In some embodiments, in block 1374, a voltage is applied to the electrode 306 through the electro - catheter 1304 ( Figure 13A ), or a voltage is applied to the electrode 1353 through the electro - catheter 1354 ( Figure 13B It should be noted that there seems to be an incomplete part in the original text after "electrode 1353( " in line 23. If you can provide the complete text, a more accurate translation can be made.) Plasma begins to be generated. Optionally, the plasma delivery tips 1301, 1351 are advanced and / or retracted to translate the lumen space 1310 along the lumen wall 1321. This may enable covering a larger area and / or making corrections in cases where the initially established lumen space 1310 is partially off-target.

[0262] The ionized gas is carried to the lumen space 1310 through the fluid conduits 1312, 1352 and returns through the fluid conduits 1311, 1353.

[0263] The generated plasma diffuses within the lumen space 1310 and may reach all locations, particularly the location of the target 1323, which may include tissue abnormalities for plasma treatment.

[0264] After the treatment is completed: At block 1375, in some embodiments, the gas may optionally be replaced with a liquid (e.g., saline) again, and then the balloons 1303A - 1303B are deflated (at block 1376) and removed.

[0265] Generally

[0266] When referring to a quantity or value herein, the term "about" means "within ±10%".

[0267] The terms "comprise", "comprising", "includes", "including", "having" and their conjugates mean "including but not limited to".

[0268] The term "consisting of" means "including and limited to".

[0269] The term "substantially consisting of" means that a composition, method or structure may include additional ingredients, steps and / or parts, but only if these additional ingredients, steps and / or parts do not substantially change the basic and novel features of the claimed composition, method or structure.

[0270] Herein, the singular forms "a", "an" and "the" include plural meanings unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" may include multiple compounds, including mixtures thereof.

[0271] The words "example" and "exemplary" are used herein to mean "as an example, instance or illustration". Any embodiment described as an "example" or "exemplary" is not necessarily to be construed as superior to or better than other embodiments and / or precluding the incorporation of features of other embodiments.

[0272] The term "optionally" is used herein to mean "provided in some embodiments and not provided in other embodiments". Any particular embodiment of the present disclosure may include a plurality of "optional" features, unless such features are in conflict.

[0273] As used herein, the term "method" refers to a way, means, technique, and procedure for accomplishing a given task, including but not limited to those ways, means, techniques, and procedures known to or developed from those known to practitioners in the fields of chemistry, pharmacology, biology, biochemistry, and medicine.

[0274] As used herein, the term "treatment" includes eliminating, substantially inhibiting, slowing down, or reversing the progression of a disease, substantially improving the clinical or aesthetic symptoms of a disease, or substantially preventing the appearance of the clinical or aesthetic symptoms of a disease.

[0275] Throughout the application, embodiments may be presented in a range format. It should be understood that the description of the range format is for convenience and brevity only and should not be construed as an inflexible limitation on the scope of the present disclosure. Accordingly, the description of a range should be considered to specifically disclose all possible sub-ranges as well as the individual values within that range. For example, the description of a range such as "from 1 to 6" should be considered to specifically disclose sub-ranges such as "from 1 to 3", "from 1 to 4", "from 1 to 5", "from 2 to 4", "from 2 to 6", "from 3 to 6", etc.; and the individual numbers within that range, e.g., 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0276] Whenever a numerical range is specified herein (e.g., "10 - 15", "10 to 15", or any pair of numbers joined by another such range indicator), it means any number (fractional or integral) within the specified range limitations, including the range limitations, unless the context clearly dictates otherwise. The terms "ranging between" a first indicator number and a second indicator number "between", and "ranging from" a first indicator number "to", "up to", "until", "through" (or another such range indicator) a second indicator number, are used interchangeably herein and mean including the first and second indicator numbers and all fractional and integral numbers therebetween.

[0277] Although the present disclosure has been described in connection with its specific embodiments, it will be apparent that many alternatives, modifications, and variations will be obvious to those skilled in the art. Accordingly, it is intended to cover all such alternatives, modifications, and variations that fall within the spirit and broad scope of the appended claims.

[0278] For clarity, certain features of the present disclosure that are described in the context of separate embodiments may also be provided combinatorially in a single embodiment, and the text will be interpreted as such a single embodiment being clearly and elaborately written. Conversely, for brevity, the various features of the present disclosure that are described in the context of a single embodiment may also be provided separately or in any suitable sub-combination or in any other described embodiment suitable for the present disclosure, and the text will be interpreted as these separate embodiments or sub-combinations having been clearly and elaborately set forth herein.

[0279] All publications, patents, and patent applications mentioned in this specification are hereby incorporated by reference in their entirety into this specification to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference herein. Additionally, the citation or identification of any reference in this application should not be construed as an admission that such reference is available as prior art to the present disclosure. With respect to the use of section headings, they should not be construed as necessarily limiting. Additionally, any priority documents of this application are hereby incorporated by reference in their entirety into this application.

Claims

1. A plasma delivery end of a medical plasma generating device, characterized in that: The device is configured to deliver the tip in vivo through a working channel of an endoscope. The plasma delivery tip includes: A gas delivery lumen defined within a circumferential wall and having a proximal - distal axis, and an ionized gas flow travels along the proximal - distal axis towards a distal aperture of the gas delivery lumen; A discharge electrode separated from the ionized gas flow by a dielectric barrier layer, which delivers a high voltage to the ionized gas flow when connected to a high - voltage source; and A check valve positioned between the discharge electrode and the distal aperture to prevent contaminants from entering a longitudinal position of the discharge electrode from the proximal end along the proximal - distal axis, thereby preventing liquid contamination in a plasma - generating region of the plasma delivery tip.

2. The plasma delivery end head according to claim 1, characterized in that: The check valve, when closed, is also positioned to prevent liquid material from entering through the distal aperture.

3. The plasma delivery end according to claim 1, wherein: The plasma delivery tip includes an expandable sheath, the expandable sheath includes a distal end configured to expand in diameter to increase a target area, and the target area can be treated simultaneously by a plasma plume emitted by the plasma delivery tip.

4. The plasma delivery tip according to any one of claims 1-3, characterized in that: The check valve opens under the pressure of the ionized gas flow.

5. The plasma delivery tip according to any one of claims 1-3, characterized in that: The check valve includes a drive valve driven separately from the pressure of the ionized gas flow.

6. The plasma delivery tip according to any one of claims 1-3, characterized in that: The distal aperture of the gas delivery lumen is inclined with respect to the proximal - distal axis.

7. The plasma delivery end head according to any one of claims 1-3, characterized in that: The check valve includes a leaf valve, a slit valve, or a flap valve.

8. The plasma delivery end head according to any one of claims 1-3, characterized in that: The check valve is configured to deflect a plasma plume generated in the ionized gas flow by a high - voltage pulse by an angle that varies according to the opening degree of the check valve.

9. The plasma delivery end according to any one of claims 1-3, characterized in that: The plasma delivery tip includes an outer peripheral wall that surrounds and is radially spaced from the circumferential wall of the gas delivery lumen to define a gap, and the ionized gas is purged through the gap after being delivered to the discharge electrode.

10. The plasma delivery end head according to any one of claims 1-3, characterized in that: The circumferential wall of the gas delivery lumen also defines a conduit through which the ionized gas is purged after being delivered to the discharge electrode.

11. The plasma delivery end according to claim 3, characterized in that: The expandable sheath includes a pre - chamber positioned along the proximal - distal axis between the discharge electrode and the distal aperture.

12. The plasma delivery tip according to claim 11, characterized in that: The pre - chamber expands to an expanded configuration having an inner diameter at least 1.5 times larger than an inner diameter of the pre - chamber in a folded configuration.

13. The plasma delivery tip according to any one of claims 2 and 11-12, characterized in that: The check valve includes a calyx having one or more vanes attached to its proximal side to the exterior of the plasma delivery tip.

14. The plasma delivery tip according to claim 13, wherein: When expanded to expose the distal aperture of the gas delivery lumen, the vanes are separated from each other.

15. The plasma delivery end head according to claim 12, wherein: The expanded configuration of the pre - chamber defines the distal aperture of the gas delivery lumen on the distal side of the pre - chamber.

16. The plasma delivery tip according to claim 12, wherein: The pre - chamber in the folded configuration includes a rigid, sharp tip configured to penetrate tissue.

17. The plasma delivery end head according to any one of claims 1-3, characterized in that: The discharge electrode extends around at least a portion of a circumference of the gas delivery lumen.

18. The plasma delivery tip according to any one of claims 1-3, characterized in that: The discharge electrode is located within the gas delivery lumen and is surrounded by the ionized gas flow.

19. The plasma delivery tip according to any one of claims 1-3, characterized in that: An outer diameter of the plasma delivery tip is less than 5 millimeters.

Images