Plasma system with multiple orientation features

Abstract

Multiple adjustable distal tips of multiple cold plasma generation devices are configured to introduce and operate within multiple narrow in vivo ranges. In some embodiments, a plasma delivery tip of a cold plasma generation device can expand from a compact delivery configuration, thereby allowing the device to operate at multiple plasma plume parameters that are difficult to achieve within the multiple dimensional constraints of a narrow delivery catheter and / or an endoscopic working channel. Additionally or alternatively, in some embodiments, multiple operating parameters of a plasma delivery tip are adjustable to adjust multiple characteristics of the plasma plume. The multiple adjustable parameters can optionally include, for example: lumen diameter, lumen aperture shape / direction, discharge electrode geometry, multiple dielectric barrier characteristics, and / or the relative placement of these components, including placement relative to an ionizing gas flow. In some embodiments, multiple plasma delivery tip elements are adapted to assist device navigation and / or tissue penetration.

Description

[0001] Related Applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 991,642, filed Mar. 19, 2020, under 35 USC § 119(e), the content of which is hereby incorporated herein by reference in its entirety.

[0003] This application is one of four co-filed applications, including a PCT application, with attorney docket numbers 85937, 85988, and 85989, the content of each of which is hereby incorporated herein by reference in its entirety.

[0004] Technical Field and Background Art

[0005] In some embodiments, the present invention relates to the field of cold atmospheric plasma generation, and more particularly to delivering cold plasma in multiple body cavities.

[0006] Plasma is a general term encompassing the multiple components of an ionized gas, typically including multiple free electrons and ions, as well as multiple neutral atoms and molecules, and typically including multiple free radicals. Plasma can be generated by gas discharge, causing multiple gas atoms or molecules to be excited and ionized. In the past decade, there has been an increasing interest in a variety of plasma applications. Some applications are based on Dielectric Barrier Discharge (DBD) to generate low-temperature, non-thermal plasma, or so-called "cold" plasma. This cold plasma is a low-ionization and non-thermal plasma generated under multiple atmospheric pressure conditions. Cold plasma has been found to be useful in various applications in medicine and industry. SUMMARY OF THE INVENTION

[0007] According to one aspect of some embodiments of the present invention, there is provided a plasma delivery tip of a medical-grade plasma generation device, the plasma delivery tip comprising: a gas delivery lumen having a proximal-to-distal axis, and an ionized gas flow flowing along the axis towards a distal orifice of the gas delivery lumen; a discharge electrode that, when attached to a high-voltage power source, transmits a high voltage to the ionized gas flow; and a dielectric barrier layer located between the discharge electrode and the ionized gas flow, wherein cold plasma is generated along the dielectric barrier layer by dielectric barrier discharge when the multiple discharge electrodes transmit the high voltage; wherein the geometry of the plasma delivery tip is dynamically adjustable to modify a parameter affecting the plasma generation.

[0008] According to some embodiments of the present invention, the plasma can be dynamically adjusted by modifying a relative position of at least two of the gas delivery lumen, the discharge electrode, and the dielectric barrier layer.

[0009] According to some embodiments of the present invention, the relative position is adjusted by moving the discharge electrode along the proximal-to-distal axis relative to the gas delivery lumen.

[0010] According to some embodiments of the present invention, the relative position is adjusted by radially offsetting the discharge electrode within the gas delivery lumen.

[0011] According to some embodiments of the present invention, the relative position is maintained by a positioning support member positioned within the gas delivery lumen.

[0012] According to some embodiments of the present invention, the relative position can be adjusted by rotating the positioning support member.

[0013] According to some embodiments of the present invention, the relative position can be adjusted by sliding the positioning support member.

[0014] According to some embodiments of the present invention, the plasma delivery tip is sized to be inserted into a target area through a hole or catheter having a diameter of 7 mm or less.

[0015] According to some embodiments of the present invention, the plasma can be dynamically adjusted by modifying a shape of at least one of the gas delivery lumen, the discharge electrode, and the dielectric barrier layer.

[0016] According to some embodiments of the present invention, the adjusted shape includes an altered diameter of the gas delivery lumen.

[0017] According to some embodiments of the present invention, the adjustment of the diameter of the gas delivery lumen is actuated by advancing the gas delivery lumen out of confinement within a sheath and allowing the elasticity of the gas delivery lumen to expand it along at least one axis to a width greater than that of the sheath.

[0018] According to some embodiments of the present invention, the adjustment of the diameter of the gas delivery lumen is actuated by a plurality of forces longitudinally applied along the proximal-to-distal axis.

[0019] According to some embodiments of the present invention, the adjustment of the diameter of the gas delivery lumen includes expanding the lumen by releasing longitudinal compression along the proximal-to-distal axis.

[0020] According to some embodiments of the present invention, the adjustment of the diameter of the gas delivery lumen includes expanding the lumen by releasing longitudinal tension along the proximal-to-distal axis.

[0021] In some embodiments of the present invention, a sheath layer is provided that circumferentially surrounds at least a portion of the dielectric barrier layer and is attached to the dielectric barrier layer on a distal side; wherein the dielectric barrier layer defines the gas delivery lumen, and a diameter of the gas delivery lumen is adjusted by adjusting a plurality of relative forces applied along an axis from a proximal side of the plasma delivery tip along the proximal side to the distal side on the sheath layer and the dielectric barrier layer.

[0022] In some embodiments of the present invention, the adjustment of the diameter of the gas delivery lumen is actuated by a plurality of forces acting circumferentially about the proximal-to-distal axis.

[0023] In some embodiments of the present invention, the discharge electrode includes a wire extending around a circumference of at least 75% of the dielectric barrier layer that defines the gas delivery lumen, and the wire is tightened to contract the dielectric barrier layer, thereby reducing a diameter of the gas delivery lumen.

[0024] In some embodiments of the present invention, the discharge electrode includes a conductive element that extends around a circumference of at least 75% of the dielectric barrier layer and is adapted to expand or contract in accordance with an increase or decrease in the diameter of the dielectric barrier layer.

[0025] In some embodiments of the present invention, the conductive element includes a conductive material deposited on an elastic support substrate.

[0026] In some embodiments of the present invention, the conductive element includes a ring having a gap that expands or contracts in accordance with an increase or decrease in the diameter of the dielectric barrier layer.

[0027] In some embodiments of the present invention, the adjusted shape includes an altered outer diameter of the gas delivery lumen.

[0028] In some embodiments of the present invention, the adjusted shape includes a shape of the discharge electrode.

[0029] In some embodiments of the present invention, the shape of the discharge electrode is adjusted to an altered length along the proximal-to-distal axis.

[0030] In some embodiments of the present invention, the shape of the discharge electrode is adjusted to an altered diameter of the discharge electrode.

[0031] In some embodiments of the present invention, the dielectric barrier includes a plurality of circumferentially arranged segments adapted to expand by radially spreading apart.

[0032] According to some embodiments of the present invention, the discharge electrode includes a plurality of circumferentially distributed segments, each segment extending along the proximal-to-distal axis.

[0033] According to some embodiments of the present invention, the discharge electrode includes a shape memory alloy that changes shape when heated to a predetermined temperature.

[0034] According to some embodiments of the present invention, the discharge electrode changes to a shape that generates less plasma when heated to the predetermined temperature.

[0035] According to some embodiments of the present invention, the discharge electrode circumferentially surrounds at least 75% of the dielectric barrier layer, and the dielectric barrier layer circumferentially surrounds the gas delivery lumen.

[0036] According to some embodiments of the present invention, a distal tip of the gas delivery lumen is beveled to form a pointed tip.

[0037] According to some embodiments of the present invention, the plasma delivery tip includes a plurality of channels extending along the proximal-to-distal axis, the plurality of channels configured to return the ionized gas in a proximal direction.

[0038] According to some embodiments of the present invention, the plurality of channels include a plurality of circumferentially separated protrusions separated by a plurality of notches around an outer surface of the plasma delivery tip.

[0039] According to some embodiments of the present invention, the plurality of channels are helical.

[0040] According to some embodiments of the present invention, the dielectric barrier layer circumferentially surrounds the discharge electrode, and the gas delivery lumen circumferentially surrounds the dielectric barrier layer.

[0041] According to one aspect of some embodiments of the present invention, a method of configuring a cold plasma plume delivered from a medical-grade plasma delivery tip is provided, the method comprising: flowing an ionized gas through a gas delivery lumen and flowing beside a discharge electrode separated from the ionized gas by a dielectric barrier layer; supplying a plurality of high-voltage electrical pulses to the discharge electrode; and adjusting at least one of the gas delivery lumen, the discharge electrode, and the dielectric barrier layer to reconfigure a plurality of plasma generation parameters of the plasma delivery tip.

[0042] According to some embodiments of the present invention, the plasma delivery tip is positioned distally on a probe catheter, and the adjustment includes actuating the change in shape from a control located proximally on the probe catheter.

[0043] According to one aspect of some embodiments of the present invention, a method of configuring a cold plasma plume delivered from a medical-grade plasma delivery tip is provided, the method comprising: advancing a plasma delivery tip distally in a folded configuration until it protrudes from a distal end of a sheath; and expanding the plasma delivery tip.

[0044] According to some embodiments of the present invention, the expanding includes expanding a gas delivery lumen of the plasma delivery tip.

[0045] According to some embodiments of the present invention, the expanding includes expanding a discharge electrode of the plasma delivery tip.

[0046] According to some embodiments of the present invention, the expanding includes increasing a thickness of an insulating barrier layer of the plasma delivery tip.

[0047] According to some embodiments of the present invention, the folded configuration of the plasma delivery tip has an outer diameter of 7 mm or less.

[0048] According to some embodiments of the present invention, the sheath is flexible.

[0049] According to some embodiments of the present invention, the sheath is rigid.

[0050] According to one aspect of some embodiments of the present invention, a plasma delivery tip of a medical-grade plasma generation device is provided, the plasma delivery tip comprising: a gas delivery lumen having a proximal-to-distal axis, and an ionized gas flow flowing along the axis towards a distal orifice of the gas delivery lumen; a discharge electrode that, when attached to a high-voltage power source, transmits a high voltage to generate plasma in the ionized gas flow; and a control operable to adjust the generation of cold plasma by modifying at least one of: a shape of at least one of the gas delivery lumen and the discharge electrode, and a relative position of the gas delivery lumen and the discharge electrode.

[0051] According to one aspect of some embodiments of the present invention, a method of configuring a cold plasma plume delivered from a medical-grade plasma delivery tip is provided, the method comprising: flowing an ionized gas through a gas delivery lumen to impinge on a discharge electrode; supplying a plurality of high-voltage electrical pulses to the discharge electrode; and during the supplying, adjusting the relative position of the gas delivery lumen and the discharge electrode to adjust the generation of cold plasma.

[0052] According to some embodiments of the present invention, the adjusting includes reorienting the discharge electrode relative to the ionized gas flow.

[0053] According to some embodiments of the present invention, the adjusting is performed on a portion of the discharge electrode located outside the gas delivery lumen.

[0054] According to some embodiments of the present invention, the adjustment is performed by moving the portion of the discharge electrode to a position offset from a longitudinal axis of a distal end of the gas delivery lumen.

[0055] According to one aspect of some embodiments of the present invention, a method of configuring a cold plasma plume delivered from a medical grade plasma delivery tip is provided, the method comprising: flowing an ionized gas through a distal portion of a gas delivery lumen to impinge on a portion of a discharge electrode; and supplying a plurality of high voltage electrical pulses to the discharge electrode; wherein the distal portion of the gas delivery lumen has a central longitudinal axis and the portion of the discharge electrode is positioned away from the longitudinal axis at a distance greater than a lumen cross-sectional radius of the gas delivery lumen.

[0056] According to one aspect of some embodiments of the present invention, a method of delivering plasma to a target surface is provided, the method comprising: positioning a distal end of a working channel within a lumen including the target surface; advancing a plasma delivery tip from the working channel along a proximal-to-distal axis of the working channel; and moving the plasma delivery tip relative to the working channel while generating at least one plasma plume directed in a direction inclined or perpendicular to the proximal-to-distal axis.

[0057] According to some embodiments of the present invention, the moving includes bending the plasma delivery tip.

[0058] According to some embodiments of the present invention, the moving includes rotating the plasma delivery tip.

[0059] According to some embodiments of the present invention, the method includes generating a plurality of plasma plumes directed in the same direction inclined or perpendicular to the proximal-to-distal axis.

[0060] According to some embodiments of the present invention, the method includes generating a plurality of plasma plumes directed in a plurality of radial directions inclined to the proximal-to-distal axis.

[0061] According to some embodiments of the present invention, the advancing releases the plasma delivery tip from a confinement lumen; a portion of the plasma delivery tip is reoriented relative to the proximal-to-distal axis upon release from the confinement lumen; and the plasma plume is generated by an ionized gas flow exiting a hole in the reoriented portion of the plasma delivery tip.

[0062] According to some embodiments of the present invention, the confinement lumen includes the working channel.

[0063] According to some embodiments of the present invention, the confinement lumen includes a sleeve that is at least partially retained within the working channel.

[0064] According to some embodiments of the present invention, the movement includes rotating the plasma delivery tip, and the rotation is performed using a plasma plume generated by a plasma generation site of the plasma delivery tip, and the plasma plume is oriented at a first angle relative to the proximal-to-distal axis; then orienting the plasma plume generated by the plasma generation site at a second angle relative to the proximal-to-distal axis.

[0065] According to some embodiments of the present invention, when the plasma plume is released from the confinement lumen, the plasma plume is reoriented between the first and second angles by a change in the curvature of the portion of the plasma delivery tip.

[0066] According to some embodiments of the present invention, the portion of the plasma delivery tip includes an elastic tube that remains straight within the confinement lumen and tends to bend when it is released from the confinement lumen.

[0067] According to one aspect of some embodiments of the present invention, there is provided a plasma delivery tip of a medical-grade plasma generation device, the plasma delivery tip including: a gas delivery lumen having a proximal-to-distal axis, and an ionized gas flow flowing along the axis to a distal orifice of the gas delivery lumen; a discharge electrode that, when attached to a high-voltage power source, transmits a high voltage to the ionized gas flow; and an electrical power conduit configured to interconnect the discharge electrode and the high-voltage power source; wherein the electrical power conduit is also adapted to receive mechanical tension to adjust the plasma delivery tip.

[0068] According to some embodiments of the present invention, the mechanical tension adjusts a steering angle of the plasma delivery tip.

[0069] According to some embodiments of the present invention, the plasma delivery tip is sized to be inserted into a target area through an orifice or catheter having a diameter of 7 mm or less.

[0070] According to one aspect of some embodiments of the present invention, there is provided a method of adjusting a plasma plume of a plasma delivery tip from a medical-grade plasma delivery device, the method including: generating a plasma plume that includes ionized gas ionized by a discharge electrode that is positioned with the plasma delivery tip and extends from an orifice of the plasma delivery tip; and adjusting an orientation of the orifice by operating a control member that bends the plasma delivery tip.

[0071] According to some embodiments of the present invention, the control member bends the plasma delivery tip, while the plasma delivery tip remains restricted within a sheath.

[0072] According to some embodiments of the present invention, the control member bends the plasma delivery tip by 15 mm or less.

[0073] According to some embodiments of the present invention, the control member bends the plasma delivery tip by rotating the plasma delivery tip within a sheath.

[0074] According to one aspect of some embodiments of the present invention, there is provided a plasma delivery tip of a medical-grade plasma generation device, the plasma delivery tip comprising: a gas delivery lumen having a proximal-to-distal axis, and an ionized gas flow flowing axially distally towards an outlet hole of the gas delivery lumen; and a discharge electrode which, when attached to a high-voltage power source, transmits a high voltage to the ionized gas flow to generate a cold plasma flow; wherein the outlet hole of the gas delivery lumen is oriented to direct a plasma plume exiting the gas delivery lumen away from the proximal-to-distal axis.

[0075] According to some embodiments of the present invention, the plasma delivery tip includes a dielectric barrier layer located between the discharge electrode and the ionized gas flow, and a cold plasma flow is generated along the dielectric barrier layer by dielectric barrier discharge when the plurality of discharge electrodes transmit the high voltage.

[0076] According to some embodiments of the present invention, the plasma delivery tip is sized to be inserted into a target area through a hole or catheter having a diameter of 7 mm or less.

[0077] According to one aspect of some embodiments of the present invention, there is provided a plasma delivery tip of a medical-grade plasma generation device, the plasma delivery tip comprising: a gas delivery lumen having a proximal-to-distal axis, and an ionized gas flow flowing along the axis towards a distal hole of the gas delivery lumen; a discharge electrode configured to ionize the ionized gas flow into a plasma; and at least one gas return channel extending along the gas delivery lumen, the ionized gas returning proximally through the gas return channel after exiting the gas delivery lumen.

[0078] According to some embodiments of the present invention, the at least one gas return channel extends helically around the gas delivery lumen.

[0079] According to some embodiments of the present invention, the gas return channel is provided with a connector to allow attachment to a negative pressure source.

[0080] According to some embodiments of the present invention, the gas return channel is open to a pressure lower than that which generates negative pressure.

[0081] According to some embodiments of the present invention, the plasma is thermally non-damaging.

[0082] According to one aspect of some embodiments of the present invention, there is provided a method of operating a plasma generating device, the method comprising: generating a plasma plume at a distal end of a lumen exiting the plasma generating device; and inserting a medical tool along the lumen until it exits the distal end.

[0083] According to some embodiments of the present invention, the method includes withdrawing an element for generating the plasma plume from the lumen before inserting the medical tool.

[0084] According to some embodiments of the present invention, the element includes a discharge electrode.

[0085] According to some embodiments of the present invention, the element includes a surface that forms and / or guides the plasma plume.

[0086] According to one aspect of some embodiments of the present invention, there is provided a plasma delivery tip of a medical grade plasma generating device, the plasma delivery tip comprising: a gas delivery lumen having a proximal-to-distal axis, and an ionized gas flow exiting through a hole in the gas delivery lumen through the axis; and a discharge electrode that, when attached to a high voltage power source through an electrical power conduit, transmits a plurality of high voltage pulses into the ionized gas flow to ionize the ionized gas into a plasma; wherein the electrical power conduit slides distally from within the gas delivery lumen to advance the discharge electrode and serves as a guide wire for guiding the advancement of the gas delivery lumen.

[0087] According to some embodiments of the present invention, the discharge electrode is encapsulated within a pointed cap.

[0088] According to some embodiments of the present invention, the electrical power conduit and the discharge electrode are configured to be withdrawn from the gas delivery lumen, thereby allowing the gas delivery lumen to serve as a working channel for delivering another tool to a distal end of the gas delivery lumen.

[0089] According to some embodiments of the present invention, the plasma is a thermally non-damaging plasma.

[0090] According to some embodiments of the present invention, the plasma delivery tip is sized to be inserted into a target area through a hole or catheter having a diameter of 7 mm or less.

[0091] According to one aspect of some embodiments of the present invention, there is provided a medical-grade plasma generation device, characterized in that: the plasma generation device includes: a first catheter through which an ionized gas stream flows out of a hole of the first catheter; and a discharge electrode which, when attached to a high-voltage power supply, transmits a plurality of high-voltage pulses into the ionized gas stream to ionize the ionized gas into a plasma; a second catheter through which the discharge electrode is advanced to an in-vivo position to generate plasma using the ionized gas stream supplied by the first catheter.

[0092] According to some embodiments of the present invention, the plasma is a heat-non-damaging plasma.

[0093] According to some embodiments of the present invention, the sizes of the first and second catheters are designed to be inserted into the in-vivo position through a hole or a third catheter with a diameter of 7 mm or less.

[0094] According to one aspect of some embodiments of the present invention, there is provided a method of constructing a discharge electrode for a medical-grade plasma device, the method including: stripping an outer insulating layer from a distal portion of a coaxial cable; replacing a flexible conductive electrical shielding layer of the distal portion of the coaxial cable with a reinforced electrical shielding layer such that a portion of a central conductor of the coaxial cable is unshielded; and insulating the unshielded portion of the central conductor with a dielectric barrier layer.

[0095] According to some embodiments of the present invention, the method includes placing an outer insulating layer back on top of the reinforced electrical shielding layer.

[0096] According to some embodiments of the present invention, the coaxial cable has an outer diameter of less than 4 mm.

[0097] According to one aspect of some embodiments of the present invention, there is provided a discharge assembly of a plasma generation device, the discharge assembly including: a coaxial cable having an outer insulator, an outer conductor, an inner insulator, and a central conductor; an electrical shielding layer that is harder than the outer conductor and extends distally from the outer conductor; and a discharge electrode within a dielectric barrier layer; wherein the discharge electrode includes a portion of the central conductor that extends distally beyond a distal end of the electrical shielding layer, and the dielectric barrier layer includes an insulator disposed separately from the inner insulator.

[0098] According to some embodiments of the present invention, the discharge assembly is provided together with the plasma generation device and is operable to generate plasma within a lumen of the plasma generation device.

[0099] According to one aspect of some embodiments of the present invention, there is provided a plasma delivery tip of a medical-grade plasma generation device for delivering plasma to a target surface outside the plasma delivery tip. The plasma delivery tip includes: a gas delivery lumen having a proximal-to-distal axis, and an ionized gas flow flows along the axis to one or more distal holes in the gas delivery lumen; and a plurality of discharge electrodes, each discharge electrode being placed to generate a corresponding plasma plume at a corresponding plasma generation site through which the ionized gas flow passes.

[0100] According to some embodiments of the present invention, the ionized gas flow through the one or more distal holes guides the plurality of plasma plumes to a plurality of different corresponding regions of the target surface.

[0101] According to some embodiments of the present invention, the plurality of plasma plumes partially overlap on their way to the target surface.

[0102] According to some embodiments of the present invention, the one or more distal holes include a plurality of separate holes, and after plasma is generated by the corresponding plurality of different discharge electrodes, the corresponding plurality of separate plasma plumes are emitted from these holes.

[0103] According to some embodiments of the present invention, the plurality of discharge electrodes include a plurality of electrodes located on a circumference of a lumen wall of the plasma delivery tip, and the ionized gas flows within the lumen wall.

[0104] According to some embodiments of the present invention, the plurality of discharge electrodes include a plurality of electrodes located within the ionized gas flow.

[0105] According to some embodiments of the present invention, the plurality of electrodes located within the ionized gas flow are circumferentially surrounded by the ionized gas flow.

[0106] According to some embodiments of the present invention, the plurality of electrodes located within the ionized gas flow are also at least partially located distally of the distal holes, and the ionized gas for generating the corresponding plasma plumes flows out from the distal holes.

[0107] According to some embodiments of the present invention, the plurality of electrodes located within the ionized gas flow are also located outside the distal holes, and the ionized gas for generating the corresponding plasma plumes flows out from the distal holes.

[0108] According to some embodiments of the present invention, the plurality of discharge electrodes are arranged along the proximal-to-distal axis of the gas delivery lumen, and the plurality of corresponding plasma plumes are guided laterally away from the axis.

[0109] According to one aspect of some embodiments of the present invention, a plasma delivery tip is provided, the plasma delivery tip comprising: a gas delivery lumen having a proximal-to-distal axis, and an ionized gas flow through the axis towards a plurality of distal holes in the gas delivery lumen; and at least one discharge electrode disposed to generate plasma within the ionized gas flow; wherein the plurality of distal holes are oriented to direct a plurality of plasma plumes emitted from the plasma delivery tip away from the proximal-to-distal axis.

[0110] According to some embodiments of the present invention, a distal portion of the gas delivery lumen is rotationally coupled to the plasma delivery tip, and the plurality of distal holes are oriented to direct the ionized gas out of them in a direction that generates a thrust, the thrust causing the distal portion of the gas lumen to rotate and causing the plurality of plasma plumes to rotate about their own axes.

[0111] According to some embodiments of the present invention, the plasma delivery tip includes a discharge electrode positioned adjacent to the rotating distal portion of the gas delivery lumen.

[0112] According to some embodiments of the present invention, the at least one discharge electrode includes a separate respective discharge electrode positioned to generate plasma at each of the plurality of distal holes.

[0113] According to some embodiments of the present invention, the plasma delivery tip includes a sliding electrical coupler through which electrical power is conducted to the distal portion of the plasma delivery tip.

[0114] According to some embodiments of the present invention, the plurality of distal holes direct the plurality of plasma plumes in a plurality of radially opposite directions.

[0115] According to some embodiments of the present invention, the plurality of distal holes direct the plurality of plasma plumes at at least two different angles away from the proximal-to-distal axis.

[0116] According to some embodiments of the present invention, the plasma delivery tip further includes a distal hole that directs a plasma plume along the proximal-to-distal axis.

[0117] According to some embodiments of the present invention, the plasma delivery tip is sized to be delivered along a working channel of an endoscopic device and is rotatable about the proximal-to-distal axis to circumferentially distribute the plasma from the plurality of plasma plumes.

[0118] According to one aspect of some embodiments of the present invention, there is provided a plasma delivery tip of a medical-grade plasma generation device for delivering plasma to a target surface external to the plasma delivery tip. The plasma delivery tip includes: a gas delivery lumen having a proximal-to-distal axis, and an ionized gas flow flows along the axis to a plurality of plasma generation sites; each plasma generation site includes an outlet hole for the ionized gas and a discharge electrode operable to generate a plasma plume from the ionized gas; and a confinement cavity that confines the plurality of plasma generation sites in a folded configuration; wherein the plurality of plasma generation sites unfold to an unfolded configuration when released from the confinement cavity, and the unfolded configuration redistributes the plurality of outlet holes into a distribution along at least one axis, the distribution being greater than the distribution of the plurality of outlet holes in the folded configuration.

[0119] According to some embodiments of the present invention, the unfolded configuration spaces each of the plurality of outlet holes apart from each other.

[0120] According to some embodiments of the present invention, the unfolded configuration aligns the plurality of outlet holes along a line.

[0121] 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 invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of various embodiments of the present invention, exemplary 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 are not meant to be limiting necessarily.

[0122] As will be understood by those skilled in the art, aspects of the present invention can be embodied as a system, method, or computer program product. Accordingly, aspects of the present invention can 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 embodiments can all be collectively referred to herein as a "circuit", "module", or "system" (e.g., a method can be implemented using a "computer circuit"). In addition, some embodiments of the present invention can take the form of a computer program product embodied in one or more computer-readable media having computer-readable program code embodied thereon. Implementations of the methods and / or systems of some embodiments of the present invention can involve performing and / or completing selected tasks manually, automatically, or a combination thereof. In addition, for actual instruments and devices of some embodiments of the methods and / or systems according to the present invention, selected tasks can be implemented by hardware, software, firmware, and / or a combination thereof, such as using an operating system.

[0123] For example, according to some embodiments of the present invention, the hardware for performing multiple selected tasks can be implemented as a chip or a circuit. As software, the multiple selected tasks according to some embodiments of the present invention can be implemented as multiple software instructions executed by a computer using any suitable operating system. In some embodiments of the present invention, one or more tasks executed in the method and / or system are executed by a data processor (also referred to herein as a "digital processor", referring to multiple data processors that operate on multiple digital bytes), such as a system platform for executing multiple instructions. Optionally, the data processor includes a volatile memory for storing multiple instructions and / or data and / or a non-volatile storage for storing multiple instructions and / or data, such as a magnetic hard disk and / or a removable medium. Optionally, a network connection is also provided. Optionally, a display and / or a user input device such as a keyboard or a mouse are also provided. Any of these implementations are more generally referred to herein as multiple examples of computer circuitry.

[0124] Any combination of one or more computer-readable media may be used in some embodiments of the present invention. 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 the computer-readable storage medium will include the following: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or 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 this program, for example, data structured in the manner recorded on the computer-readable storage medium so that a computer program can access it, for example, one or more tables, lists, arrays, data trees, and / or another data structure. In this document, a computer-readable storage medium that records data in a retrievable form as a plurality of digital bytes is also referred to as a digital memory. It should be understood that in some embodiments, a computer-readable storage medium optionally also serves as a computer-writable storage medium when the computer-readable storage medium is not inherently read-only and / or in a read-only state.

[0125] In this document, a data processor is said to be "configured" to perform a plurality of data processing actions if it is coupled to a computer-readable memory to receive a plurality of instructions and / or data therefrom, process them, and / or store a plurality of processing results in the same or another computer-readable memory. The processing performed (optionally the processing performed on data) is specified by the plurality of instructions, the effect of which is that the processor operates in accordance with the plurality of instructions. The actions of the processing may alternatively or additionally be referred to by one or more other terms; for example: compare, estimate, determine, calculate, identify, combine, store, analyze, select, and / or transform. For example, in some embodiments, a digital processor receives a plurality of instructions and data from a digital memory, processes the data in accordance with the plurality of instructions, and / or stores a plurality of processing results in the digital memory. In some embodiments, "providing" a plurality of processing results includes transmitting, storing, and / or presenting one or more of the plurality of processing results. Presenting optionally includes displaying on a display, indicating by sound, printing on a printout, or otherwise giving the plurality of results in a form accessible to a variety of human sensory capabilities.

[0126] A computer-readable signal medium may include, for example, a propagated data signal that includes computer-readable program code, either in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including but not limited to electromagnetic, optical, or any suitable combination of the foregoing. A computer-readable signal medium may be any computer-readable medium that is not a computer-readable storage medium and that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.

[0127] The program code and / or data used thereby included on a computer-readable medium may be transmitted using any appropriate medium, including but not limited to wireless, wired, fiber optic cable, RF, etc., or any suitable combination of the foregoing.

[0128] Computer program code for performing the operations of some embodiments of the present invention may be written in any combination of one or more programming languages, including object-oriented programming languages such as Java, Smalltalk, C++, etc. and conventional procedural programming languages such as the "C" programming language or various similar programming languages. The program code may 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 may 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 may establish a connection with an external computer (e.g., through the Internet using an Internet service provider).

[0129] Some embodiments of the present invention may be described below with reference to the flowcharts and / or block diagrams of various methods, devices (systems), and computer program products according to some embodiments of the present invention. It should be understood that each block of the flowcharts and / or block diagrams, and combinations of blocks in the flowcharts and / or block diagrams, can be implemented by computer program instructions. These computer program instructions may 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 processor of the computer or other programmable data processing apparatus create means for implementing the functions / actions specified in the block or blocks of the flowchart and / or block diagram.

[0130] These computer program instructions may 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 that includes instructions for implementing the functions / actions specified in the block or blocks of the flowchart and / or block diagram.

[0131] 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 processes for implementing the functions / actions specified in the block or blocks of the flowchart and / or block diagram. BRIEF DESCRIPTION OF THE DRAWINGS

[0132] Some embodiments of the present invention are described herein by way of example only with reference to the multiple figures. Now, specifically referring in detail to the multiple figures, it is emphasized that the multiple details shown are by way of example and for the purpose of illustrative discussion of the multiple embodiments of the present invention. In this regard, for those skilled in the art, the description in conjunction with the multiple figures makes it obvious how to implement the multiple embodiments of the present invention.

[0133] In the multiple figures:

[0134] Figure 1A Schematically represents a plasma processing apparatus according to some embodiments of the present invention;

[0135] Figure 1B Schematically represents a plasma delivery tip configured with an adjustable lumen diameter according to some embodiments of the present invention;

[0136] Figure 1C Schematically represents a plasma delivery tip configured with a tension-adjustable lumen wall thickness according to some embodiments of the present invention;

[0137] Figure 1D Schematically represents a plasma delivery tip configured with co-adjustable lumen wall thickness and lumen diameter according to some embodiments of the present invention;

[0138] Figure 1E Schematically represents a plasma delivery tip configured with telescopically adjustable lumen wall thickness and lumen diameter according to some embodiments of the present invention;

[0139] Figure 1F Schematically represents a plasma delivery tip configured with a twist-adjustable lumen diameter according to some embodiments of the present invention;

[0140] Figure 1G Schematically represents a plasma delivery tip configured with a twist-adjustable lumen diameter according to some embodiments of the present invention;

[0141] Figure 1H Schematically shows in cross-section multiple different thermal measurement device configurations for use with a plasma delivery tip according to some embodiments of the present invention;

[0142] Figure 2A Schematically represents a plasma delivery tip configured with an adjustable-length plasma discharge electrode according to some embodiments of the present invention;

[0143] Figure 2BSchematically shows a plasma delivery tip configured with a plasma discharge electrode of adjustable diameter according to some embodiments of the present invention;

[0144] Figure 2C Schematically shows according to some embodiments of the present invention Figure 2B a front view of one end of the plasma discharge electrode of adjustable diameter;

[0145] Figure 2D Schematically shows a plasma delivery tip configured with a plasma discharge electrode of adjustable diameter according to some embodiments of the present invention;

[0146] Figure 2E Schematically shows a plasma delivery tip configured with a lasso - type plasma discharge electrode of adjustable diameter according to some embodiments of the present invention;

[0147] Figure 2F Schematically shows a plasma delivery tip configured with an open - loop type plasma discharge electrode of adjustable diameter according to some embodiments of the present invention;

[0148] Figure 2G Schematically shows a plasma delivery tip configured with a helical - type plasma discharge electrode of adjustable length according to some embodiments of the present invention;

[0149] Figures 2H to 2J Schematically shows a plasma delivery tip configured with a segmented - expansion distal end according to some embodiments of the present invention;

[0150] Figure 3A Schematically shows a plasma delivery tip configured with a manipulable end according to some embodiments of the present invention;

[0151] Figure 3B Schematically shows a plasma delivery tip configured with an end, the end being configured to contract into a piercing cone;

[0152] Figure 4 Schematically shows a plasma delivery tip configured with a beveled distal end according to some embodiments of the present invention;

[0153] Figure 5A Schematically shows a plasma delivery tip configured with a channel insulating tube according to some embodiments of the present invention;

[0154] Figure 5B Schematically shows a plasma delivery tip configured with a helical channel insulating tube according to some embodiments of the present invention;

[0155] Figure 5C Schematically shows according to some embodiments of the present inventionFigures 5A to 5B An end view of a cross-section of the channel insulating tube;

[0156] Figure 5D Schematically shows a plasma delivery tip configured with a helical channel insulating tube according to some embodiments of the present invention;

[0157] Figure 6A Schematically shows a plasma delivery tip including a discharge electrode assembly according to some embodiments of the present invention, the discharge electrode assembly being positioned within a lumen of a gas supply tube;

[0158] Figure 6B Schematically shows multiple position adjustments of the discharge electrode within a plasma delivery tip according to some embodiments of the present invention;

[0159] Figures 6C to 6D Schematically shows a positioning support configured to be used with a plasma delivery tip according to some embodiments of the present invention, the plasma delivery tip including a discharge electrode assembly positioned within a lumen of a gas supply tube;

[0160] Figures 6E to 6G Schematically shows a positioning support that allows longitudinal and radial position adjustment of a plasma delivery tip, the plasma delivery tip including a discharge electrode assembly positioned within a lumen of a gas supply tube;

[0161] Figures 7A to 7D Schematically shows multiple adjustable discharge electrodes of various discharge electrode assemblies configured to be positioned within a lumen of a gas supply tube according to some embodiments of the present invention;

[0162] Figure 8A Schematically shows a discharge electrode assembly configured to be positioned within a lumen of a plasma gas supply tube and including a dielectric barrier layer adjustable by inflation according to some embodiments of the present invention;

[0163] Figure 8B Schematically shows a discharge electrode assembly configured to be positioned within a lumen of a plasma gas supply tube and including a multi-thin-layer dielectric barrier layer according to some embodiments of the present invention;

[0164] Figure 9 Schematically shows a discharge electrode assembly and a coaxial cable (an example of a coaxial cable) configured to be used as a guide wire for guiding a gas supply tube forward according to some embodiments of the present invention;

[0165] Figures 10A to 10C Schematically shows the optional use of multiple alternative tools with a gas supply tube according to some embodiments of the present invention;

[0166] Figures 11A to 11D Schematically shows various different arrangements of a plurality of lumens for ionized gas delivery, plasma / ionized gas removal, and / or current delivery according to some embodiments of the present invention;

[0167] Figures 12A to 12B Schematically shows various structural details of a small-diameter discharge electrode assembly according to some embodiments of the present invention;

[0168] Figures 13A to 13F Schematically shows a plurality of plasma delivery tips configured to generate an inclined and / or perpendicular angle with respect to a longitudinal axis of the plasma delivery tip according to some embodiments of the present invention;

[0169] Figure 14A Schematically shows the scanned delivery of cold plasma to a single cavity according to some embodiments of the present invention;

[0170] Figure 14B Schematically shows a plasma delivery tip configured for angular scanning from within a sheath according to some embodiments of the present invention;

[0171] Figure 14C Schematically shows a plasma delivery tip configured for wire-guided scanning by bending a gas delivery tube according to some embodiments of the present invention;

[0172] Figures 15A to 15C Schematically shows a plasma delivery tip configured for rotational actuation scanning of a plasma plume according to some embodiments of the present invention;

[0173] Figure 16 Is a schematic flowchart of a method for adjusting a plasma delivery tip according to some embodiments of the present invention;

[0174] Figures 17A to 17D Shows a plasma delivery tip according to some embodiments of the present invention, which expands its distal holes to a cross-section wider than the diameter of the sheath of the expanded tip;

[0175] Figures 18A to 18D Shows other examples of a plurality of wide cross-section distal holes according to some embodiments of the present invention;

[0176] Figures 19A to 19F Shows examples of wide cross-section distal holes of a plurality of plasma delivery tip tubes that themselves accommodate a plurality of discharge electrode assemblies having a plurality of elongated cross-sections according to some embodiments of the present invention;

[0177] Figures 20A to 20CSchematically shows a width-expanded discharge electrode assembly for use with a plasma delivery tip according to some embodiments of the present invention;

[0178] Figures 21A to 21B Schematically shows a differently width-expanded discharge electrode assembly for use with a plasma delivery tip according to some embodiments of the present invention;

[0179] Figures 22A to 22C Schematically shows a flow-diffused electrode assembly for use with a plasma delivery tip according to some embodiments of the present invention;

[0180] Figures 23A to 23B Schematically shows an off-axis-expanded discharge electrode assembly for use with a plasma delivery tip according to some embodiments of the present invention;

[0181] Figures 24A to 24C Schematically shows an off-axis-expanded electrode assembly for use with a plasma delivery tip having an off-axis-oriented ionization gas outlet hole according to some embodiments of the present invention;

[0182] Figure 25 Schematically shows an off-axis-expanded discharge electrode assembly for use with a plasma delivery tip according to some embodiments of the present invention;

[0183] Figure 26 Schematically shows a self-expanding discharge electrode assembly for use with a plasma delivery tip according to some embodiments of the present invention;

[0184] Figures 27A to 27B Schematically shows a self-expanding discharge electrode assembly for use with a plasma delivery tip according to some embodiments of the present invention;

[0185] Figures 28A to 28C Schematically shows according to some embodiments of the present invention and Figures 27A to 27B A plasma delivery tip that encapsulates the self-expanding discharge electrode assembly differently as shown;

[0186] Figures 29A to 29B Schematically shows a plurality of plasma delivery tips delivered through a working channel within a sleeve according to some embodiments of the present invention;

[0187] Figures 30A to 30B Schematically represents a mode of plasma interaction with a surface according to some embodiments of the present invention, the surface being generated by rotating a longitudinal axis about a longitudinal axis that is offset and / or tilted from the longitudinal axis of the plasma plume itself;

[0188] Figures 31A to 31CSchematically depicts a self - aligning plasma delivery tip according to some embodiments of the present invention, which can be actuated to re - orient a plasma exit hole through a range of multiple off - axis orientations relative to a longitudinal axis of the sleeve and / or the working channel through which it is delivered;

[0189] Figures 32A to 32C Schematically depicts a self - aligning plasma delivery tip according to some embodiments of the present invention, which can be actuated to re - orient a plasma exit hole through a range of multiple off - axis orientations relative to a longitudinal axis of the sleeve and / or the working channel through which it is delivered;

[0190] Figures 33A to 33C Schematically depicts a self - aligning plasma delivery tip according to some embodiments of the present invention, which can be actuated to re - orient a plasma exit hole through a series of multiple off - axis orientations relative to a longitudinal axis of the sleeve and / or the working channel through which it is delivered;

[0191] Figures 34A to 34B Schematically shows a plasma delivery tip provided with a plurality of discharge electrode assemblies according to some embodiments of the present invention;

[0192] Figure 35 Shows the plasma delivery tip operating in a manipulable configuration according to some embodiments of the present invention Figures 34A to 34B of;

[0193] Figures 36A to 36B Schematically shows a plasma delivery tip provided with a plurality of discharge electrode assemblies according to some embodiments of the present invention, the plurality of discharge electrode assemblies being operable with a corresponding plurality of individual gas supply tubes;

[0194] Figure 37 and 39 Schematically shows a plasma delivery tip provided with a plurality of discharge electrode assemblies according to some embodiments of the present invention, the plurality of discharge electrode assemblies being operable with a corresponding plurality of individual gas supply tubes that expand into a radially expanding shape when advanced from a constriction;

[0195] Figure 38 Schematically shows a plasma delivery tip provided with a plurality of discharge electrode assemblies according to some embodiments of the present invention, the plurality of discharge electrode assemblies being operable with a corresponding plurality of individual gas supply tubes that are linearly arranged and branch out from a common lumen of the gas supply tubes;

[0196] Figures 40A to 40C Schematically shows a manifold - type plasma delivery tip according to some embodiments of the present invention;

[0197] Figure 41Another manifold plasma delivery tip according to some embodiments of the present invention is schematically shown;

[0198] Figures 42 to 43 schematically shows an additional manifold plasma delivery tip according to some embodiments of the present invention;

[0199] Figure 44 , 45A 45B and 46A to 46B schematically illustrate various embodiments of multiple self-spinning plasma delivery tips according to some embodiments of the present invention;

[0200] Figures 47A to 47C and 48 schematically show alternative embodiments of internal components of self-spinning plasma delivery tips according to some embodiments of the present invention; and

[0201] Figure 49 and 50 A plasma delivery tip configured with a plurality of longitudinally spaced plasma generation sites is schematically shown in accordance with some embodiments of the present invention. DETAILED DESCRIPTION

[0202] The present invention, in some embodiments thereof, relates to the field of cold atmospheric plasma generation and, more particularly, to the delivery of cold plasma within multiple body cavities.

[0203] Overview

[0204] A broad aspect of some embodiments of the present invention is directed to methods and devices for providing cold (non-thermal) plasma to living tissue under conditions of medically acceptable temperature, safety, and sterility (i.e., the devices are medical-grade plasma generating devices); and in particular, at a temperature that remains below a threshold of thermal damage and / or protein denaturation. Medical-grade plasma generating devices that generate plasma below the threshold of complete thermal destruction of cellular structures are also referred to herein as "thermally atraumatic" medical-grade plasma generating devices.

[0205] Thermal coagulation is considered to occur above 60 °C. Some proteins may denature or otherwise be functionally impaired at multiple temperatures well below 60 °C; for example, even at multiple slightly elevated ("fever") temperatures around 40 °C. However, multiple temperatures moderately below 60 °C, such as 50 °C, can be applied for multiple limited times without causing significant thermal damage (e.g., about 1 to 2 minutes; potentially longer, depending on the total thermal energy applied to the biological target and the rate of heat transfer out). Multiple colder temperatures (e.g., about 40 to 45 °C) can generally be applied to a local area for multiple longer times without causing thermal damage. The plasma generated at any of these temperatures can be considered "cold" or "non-thermal" because the plasma is not in thermal equilibrium when it is generated - the electrons in the plasma may have very high-temperature energies (e.g., thousands of degrees Celsius), while the much heavier ions remain cold.

[0206] In a variety of biological applications, a plasma that is "cold" in the sense of the equilibrium can still be classified into hotter plasmas (e.g., at 60 °C or above 60 °C) according to its multiple effects. Due to thermal damage, the plasma will immediately cause multiple structural changes in tissues, as well as applying colder plasmas (e.g., at 50 °C or below 50 °C) to avoid thermal damage. The multiple main effects of this type of colder plasma are mediated by multiple chemical reactions caused by the presence of ionic atoms and / or molecular species. Potentially, the cold plasma of the type without thermal damage has multiple therapeutic effects involving the damage or alteration (different from the complete destruction) of multiple biological pathways. For example, it can act to destroy and / or trigger the destruction of multiple tumor cells and / or multiple pathogens (e.g., multiple virus particles, multiple bacteria, multiple fungi, and / or multiple infectious protein particles). Due to being chemically reactive in nature, this destruction may be more selective than thermal destruction, for example, having multiple different effects on multiple healthy cells and multiple abnormal cells and / or multiple invasive pathogens.

[0207] A proposed mechanism for the therapeutic effects generated by these reactions involves sensitivity to multiple free radicals. In some cases, there may be a different sensitivity; that is, a target tumor and / or pathogen is more sensitive to multiple free radicals than the nearby healthy tissue. The multiple treatment effects may depend on the multiple interactions between the multiple parameters of the target (e.g., surrounding fluid, target size, and / or target type) and the multiple parameters of the delivered plasma (e.g., generated ionized substances, their multiple concentrations, and / or multiple ratios). The multiple parameters of the plasma delivered in sequence may be affected by the multiple parameters of the plasma generation (e.g., ionization medium composition and / or multiple electrical parameters) and the multiple parameters of the plasma plume itself (e.g., geometry, containment, flow, and / or quenching).

[0208] The multiple parameters of plasma generation that produce these therapeutic effects may vary significantly between multiple different plasma generator designs, an ionized gas used as a medium, multiple contents of the generated plasma, the environment, tumor / pathogen size, and / or tumor / pathogen type. Therefore, it is a potential advantage for a plasma delivery device to be operable under a range of multiple operating parameters.

[0209] In this document, "plasma" and "plasma plume" more specifically refer to cold plasma, which is also non-thermal; that is, the plasma is delivered at a temperature of 50 °C or lower, preferably within or below the range of multiple heating temperatures (e.g., below 45 °C), and optionally at multiple temperatures equal to or even lower than normal human body temperature, such as within a range of about 20 °C to 30 °C. The cold plasma is typically delivered under conditions of approximately atmospheric pressure and is thus also referred to as "cold atmospheric plasma" or CAP. The plasma plume is generated from a supply of "ionized gas", which optionally includes any suitable mixture of atomic and / or molecular species (including a single species) that can be ionized to generate cold plasma. Multiple typical ionized gas mixtures include one or more noble gases, which are optionally mixed with other substances such as multiple molecules of nitrogen, oxygen, and / or water.

[0210] In some embodiments, the tissue target to which the cold plasma is delivered is inside a living body. Optionally, the target is outside a living body, and optionally, the target is not part of a living human body. For example, the target is optionally a calibration target, such as a target equipped to characterize plasma generation under multiple different settings of the plasma delivery device, optionally including multiple different parameter settings of the plasma delivery tip; for example: multiple different dielectric barrier thicknesses, multiple different gas delivery lumen diameters, and / or multiple different discharge electrode widths. Additionally or alternatively, the target is a measurement target; for example, a target for in vitro and / or ex vivo measurement of multiple cold plasma effects (e.g., under multiple conditions of multiple different parameter settings of the plasma delivery tip) on one or more types of, for example: multiple tumor cells, multiple pathogen cells, multiple infectious particles (multiple viruses or multiple infectious protein particles), multiple healthy cells, and / or multiple tissue samples.

[0211] Cold plasma is generated in a non-equilibrium state, and its ionization state rapidly decays as the charged species interact with each other, with other substances in the ionized gas, and / or with the environment.

[0212] In some embodiments, a high-voltage discharge electrode operating in an ionized gas environment near the target generates a cold plasma plume (e.g., having a length of about 1 to 20 mm). A potential advantage of generating the plasma very close to its target is to reduce plasma degradation due to, for example, interaction with multiple catheter walls. The non-equilibrium state is characterized by the cold plasma being weakly ionized. For some cold plasmas, the ionization is estimated (within a factor of about 10) to be on the order of a few parts per million and / or 10 11 to 10 13 electrons / cm 3 . The generated plasma is carried towards the target by the flow of the ionized gas.

[0213] These operating conditions impose potentially conflicting constraints on the device design.

[0214] One constraint is size. Optionally, a relatively small diameter (e.g., 5 mm or less, 6 mm or less, 7 mm or less, or other diameters) of the distal tip of a plasma generating device is used to facilitate an internal body access path that allows the plasma to be applied to the tissue target (the plasma is also generated at the tip). The small-diameter plasma generating tip itself can be introduced into the target, for example, using a catheter sheath and / or an endoscope working channel.

[0215] Another constraint is temperature. In some embodiments of the present invention, plasma generation includes delivering electrical power into a high-voltage gradient electric field through which a gas containing one or more easily ionizable atomic and / or molecular species flows. Briefly, the steep voltage gradient of the electric field tears multiple atoms into multiple ions and multiple free electrons. This in turn creates a cascade effect as multiple high-energy free electrons transfer portions of their energy to other still-bound electrons while also releasing them. The multiple free electrons move at a high temperature (possibly thousands of Kelvin degrees); however, the thermal mass they provide to the plasma is very small. The plasma is considered "cold" when the multiple heavier atomic ions themselves remain around room temperature (moving relatively slowly). The typical goal of cold plasma generation in various medical applications is to keep the bulk plasma temperature at 40 °C or lower (e.g., below the multiple protein denaturation temperatures), or 50 °C or lower. In some embodiments of the present invention, the plasma temperature is below body temperature and optionally at room temperature, for example, within a range of 20 to 35 °C, and optionally within a range of about 24 to 25 °C. Such thermal conditions can be enhanced, for example, by removing heat from the system at a sufficient rate to overcome the thermal effects of the input electrical power. One way to do this is to maintain a continuous flow of the supply of the ionized gas (thus acting as its own coolant). In some embodiments, waste ionized gas is also removed.

[0216] Another limitation is electrical safety. Multiple high voltages tend to generate multiple high currents, thus posing a potentially serious safety problem for a variety of medical applications. In some embodiments, a plasma is generated by the method of dielectric barrier discharge (DBD) to reduce the safety problem. In this method, a dielectric barrier (such as an electrical insulator) is located between the high-voltage electrode and the ground. Then a pulsed voltage can be used to effect dielectric barrier discharge, for example, a plurality of pulses including radio frequency and / or microwave frequencies. The ionized gas flowing along the dielectric barrier on the side opposite the discharge electrode is thus affected by a varying plurality of electric fields, which are capable of stripping some electrons from their atoms, thereby generating a plurality of free electrons. The plurality of free electrons collect energy from the electric fields to form a discharge current; a displacement current is also generated through the dielectric material. The actual power transferred to the ionized gas is relatively small, so even if some of the plurality of electrons are accelerated to higher temperatures, the generated plasma remains "cold" overall.

[0217] According to some embodiments, since the internal electrode is insulated, the plurality of pulses are configured not to be dangerous to the patient. For internal body use, the electrical ground is optionally provided by the tissue itself - because the dielectric barrier discharge current is very low. In addition, the plurality of high-frequency pulses present high voltage in a very short time (e.g., on a nanosecond time scale), making them safer for the patient compared to long-duration pulses. Compared to separate single voltage pulses or RF pulses at 10 kHz frequency, RF pulses at MHz frequency may require a lower voltage amplitude to initiate the plasma, thus increasing the safety of the device.

[0218] It should be understood that the dielectric barrier itself is not necessary for the generation of the plasma. In some embodiments, a dielectric barrier layer is omitted, shorting the ionized gas to the discharge electrode. In such embodiments, the safety provided by the plurality of current-limiting effects associated with DBD does not exist. Optionally, protection uses a control-based method; for example, the detection of a plurality of overcurrent events (arcs) is coupled to a rapid shutdown of the supplied high voltage.

[0219] The various embodiments described herein include the dielectric barrier layer, but it should be understood that, at least from an electrical perspective, the dielectric barrier layer is optionally removed. Of course, this removes from the various embodiments a number of features related to the various modified properties of the dielectric barrier layer (such as the thickness). Optionally, a number of features described herein are retained, the number of features depending on the mechanical attachment of the dielectric barrier layer to cause changes in the lengths and / or thicknesses of a number of other features, for example, by substituting a material (such as a metal) or design (such as a perforated polymer) that does not act as a dielectric barrier layer. Potential advantages of removing the dielectric barrier layer include reducing the total thickness (outer diameter) for a given gas delivery lumen size (inner diameter), and reducing the breakdown voltage, thereby allowing a lower voltage to be used at the discharge electrode.

[0220] One aspect of some embodiments of the present invention relates to a number of plasma device tips having a number of dynamically configurable functional parameters that affect the generation and / or delivery of plasma (i.e., the parameters of the number of plasma device tips are modifiable to regulate cold plasma generation). Potential advantages of the number of dynamically configurable functional parameters include: maintaining electrical and / or thermal safety, adjusting the number of requirements and / or limitations for a given target and / or target site, and / or adjusting the use of a particular ionized gas (such as a particular mixture and / or pressure of atomic and / or molecular species).

[0221] In some embodiments, a plasma device tip is configured to allow modification of one or more plasma plume generation parameters of the device; for example:

[0222] · A gas delivery lumen diameter,

[0223] · A dielectric barrier resistance and / or impedance,

[0224] · Discharge electrode geometry,

[0225] · Discharge electrode placement (relative to an ionized gas flow), and / or

[0226] · The direction and / or velocity of the ionized gas flow.

[0227] Multiple adjustments are optionally within a range of a factor of about ±5% around a central value, ±12% around a central value, ±25% around a central value, ±50% around a central value, or other ranges. In some embodiments, the multiple adjustments are performed using multiple independent adjustment mechanisms. In some embodiments, a single adjustment mechanism coordinately adjusts two or more plasma generation parameters. In some embodiments, once at the site of cold plasma delivery, the plasma delivery tip size (e.g., diameter) is adjustable (e.g., expandable, optionally expandable from a minimum size for delivery) to change its multiple electrical characteristics to be more suitable for safe in vivo cold plasma delivery. In some embodiments, one or more plasma delivery tip characteristics are adjusted to tune the generation of the plasma plume to the particular treatment environment and / or a particular target treatment. A conceptually "perfect" setting for generating plasma in a particular environment may be variable and / or unknown in advance - e.g., affected by multiple factors such as heat accumulation and dissipation rates, target geometry, and / or target accessibility.

[0228] In some embodiments of the present invention, the plasma delivery tip is configured to access multiple in vivo target regions through multiple lumens and / or multiple holes, such as: about 15 mm or less, about 10 mm or less, about 5 mm or less, about 4 mm or less, or about 3 mm or less. The diameter of a gas delivery lumen delivers the ionizable gas to be ionized into plasma at the plasma delivery tip and / or delivers the ionizable gas itself as a plasma plume exiting the plasma delivery tip, optionally within multiple ranges between about 0.4 mm and 8 mm. The length of the portion of the plasma delivery tip that generates and shapes the plasma plume is optionally between about 4 mm and 30 mm. Multiple longer lengths optionally use multiple correspondingly higher discharge voltages to prevent dielectric breakdown.

[0229] It can be understood that limiting the physical size of the plasma generation tip of a plasma delivery device (e.g., limited to a size that can be inserted through or as a catheter, and / or a size on the working channel of an endoscope) thus imposes multiple limitations on the multiple plasma generation parameters of the device and / or on the thermal, ionization, and / or geometric characteristics of the generated plasma plume.

[0230] As the tip size decreases, for a given amount of delivered ionization electrical power, the temperature tends to increase (i.e., as the power density increases); for example, as long as the power is delivered to a more concentrated area. Additionally, a smaller tip size will limit the gas flow through the tip, which can also lead to an increase in temperature due to loss of multiple coolant effects. Multiple factors such as these tend to push the multiple operating temperatures towards the top of the allowable range (e.g., towards 40 °C). However, as the tip size (and thus its thermal mass) decreases, the multiple thermal characteristics of a potentially variable operating environment become increasingly important for determining the equilibrium temperature of the device during operation. For a device with multiple electrostatic parameters, it may be difficult to ensure delivery of multiple therapeutically effective amounts of plasma while maintaining an adequate thermal safety margin for all such operating environments.

[0231] Keeping the power delivery near (while staying below) multiple current thermal limits is a potential advantage. As the multiple thermal limits change (e.g., as a function of the multiple thermal characteristics of the environment and / or the device), a target power delivery level may change accordingly. One way to affect the power is to adjust the axial length of the part of a generated electric field that is effective for plasma generation. In some embodiments of the present invention, this is achieved at least in part by increasing / decreasing a discharge electrode length.

[0232] Another way to affect the power is to increase the voltage delivered to the discharge electrode. However, in multiple embodiments operating by dielectric barrier discharge, the voltage should be set below the breakdown voltage of the dielectric barrier.

[0233] As the probe size decreases, the multiple requirements for the dielectric barrier thickness may limit the minimum practical device size (e.g., minimum diameter). Exceeding the breakdown voltage can result in, for example, temporary device shutdown and / or a safety issue. Making the dielectric barrier too thick may interfere with plasma generation at multiple lower voltages, and / or result in a reduced gas lumen size (i.e., in multiple embodiments where the physical thickness of a dielectric barrier is increased to increase its breakdown voltage). Multiple materials suitable for use as the dielectric barrier include multiple materials with a dielectric constant up to about 6 to 8 and / or a dielectric strength of about 10 to 10 kV / mm or higher. In some embodiments, the dielectric barrier wall thickness is in a range between about 0.07 mm and 1.5 mm.

[0234] Multiple rigid dielectric materials include ceramics, quartz, and certain glasses (e.g., Pyrex TM)。Potential multiple elastic dielectric materials include, for example, PEEK (polyether ether ketone), PTFE (polytetrafluoroethylene), ABS (acetonitrile betainestyrene), TPU / TPE (thermoplastic polyurethan, or more generally multiple thermoplastic elastomers), nylon, and / or PVC (polyvinylchloride).

[0235] In some embodiments of the present invention, the dielectric barrier thickness is adjustable; for example, allowing multiple barrier characteristics to be matched with the multiple barrier characteristics required to operate at a currently selected discharge voltage. The barrier thickness can be adjusted by adjusting the layer thickness (e.g., the layer thickness of an elastic barrier material) and / or by adjusting the number of layers (e.g., the number of layers of elastic and / or rigid barrier materials).

[0236] The energy release from the discharge electrode is affected by the length or width of the ionization region. For example, a longitudinally shorter discharge electrode may produce less ionization effect than a longer discharge electrode. Optionally, this is adjusted in some embodiments by adjusting the length of the discharge electrode (e.g., how much of the distal end of a core conductor of a coaxial cable, or another discharge electrode design is unshielded).

[0237] Additionally or alternatively, in some embodiments, the positioning (distance and / or angle) of the discharge electrode relative to an air flow is adjusted. This optionally includes positioning the discharge electrode outside the conduit through which the ionization gas is introduced, for example, by adding a control member that allows the discharge to be advanced at least a few millimeters or centimeters beyond a hole for supplying the ionization gas. This can be the same hole used to convey the discharge electrode itself, or a different hole. As it advances beyond the multiple ranges of a plasma delivery tip or the lumen of a working channel, a discharge electrode may change its shape and / or orientation. For example, it can include a superelastic alloy configured to assume a preset shape when released from confinement.

[0238] Then, the ionization region becomes, in part, a function of the location where the ionized gas stream intersects multiple portions of the discharge electrode. If the ionized gas flows substantially perpendicular to a longitudinal axis of the discharge electrode, a relatively short ionization region may exist. If the ionized gas flows substantially along the longitudinal axis of the discharge electrode, a relatively long ionization region may exist. In addition to its length (i.e., length along a longitudinal axis), a discharge electrode may be relatively wide or narrow. Depending on the ionized gas stream, a relatively large discharge electrode width may establish a correspondingly larger ionization region.

[0239] Additionally or alternatively, control of the intersecting region can be achieved by redirecting the ionized gas stream, by positioning the discharge electrode closer to or farther from the ionized gas stream, and / or by orienting the discharge electrode such that the ionized gas stream intersects a larger or smaller extent of the discharge electrode.

[0240] It should be noted that the directionality of the ionized gas stream outside the lumen is optionally controlled at either of its "ends".

[0241] At the proximal side (the outflowing hole), the main direction of the flow can be redirected by redirecting a hole and / or a baffle.

[0242] At the distal side (outside the environment), the flow is affected by nearby structures; for example, by the proximity and / or relative orientation of a tissue surface including a treatment target. When it approaches a surface, the flow can be converted into a direction that is more nearly parallel to the surface - even if it starts at an angle substantially perpendicular to it. A surface of the environment can also partially serve to restrict the flow of the plasma. For example, plasma can be generated on either side of a plate-shaped electrode (flat, but relatively wide and long) through which the ionized gas flows. If one side is brought close to a tissue target, the surface of the target (and the surrounding area) tends to restrict the plasma generated on that side, thereby potentially increasing its concentration.

[0243] The cold plasma concentration is affected by the length of time (as a duration) of the ionized gas flow in the ionization region, making it a potential function of the geometry (e.g., length and width) of the ionization region and the velocity of the gas flow. For a given pressure of the supplied ionized gas, as the gas flow accelerates, a smaller diameter tip lumen may reduce the concentration of the plasma ions. However, the final plasma concentration may increase due to restricting the diameter of the lumen. Conversely, an increase in the ionized gas flow (with the diameter remaining unchanged) may increase the power while reducing the plume temperature. Thus, an optimal diameter adjustment for plasma concentration may be neither at the minimum diameter nor at the maximum diameter, which can be determined by multiple trial adjustments and multiple observations.

[0244] When generating plasma in a lumen - for a given lumen diameter (with other plasma generation parameters, such as ionized gas composition and / or flow rate being equal), there is a corresponding distance - typically equal to several lumen diameters - along which the current and power carried by the plasma plume (if not quenched) are approximately constant. Beyond this length, the power delivery decreases. Similarly, the plasma temperature tends to be approximately constant along an initial portion of the plasma plume. However, near the tip, the tapering of the plasma plume may increase the current density and / or temperature. The plasma regions with more constant current, power, and / or temperature may be more preferred for treatment - for example, their parameters are more controllable, and they may be safer and / or more effective.

[0245] The plasma generated outside the lumen (e.g., at an intersection between an unrestricted flow and a properly positioned discharge electrode) can reflect the same general observations in the lumen-generated plasma: the plasma at a certain distance from the discharge electrode is colder or more suitable for tissue treatment than the plasma at a short distance. Thus, a potential advantage of using an "outside-lumen" electrode (i.e., a discharge electrode located in an ionized gas flow not restricted by its delivery lumen) is that it can be arbitrarily close to the tissue target.

[0246] In addition, in some embodiments, multiple adjustments are made to the geometry of the discharge electrode, which helps to control the distances at which the generated plasma contacts the tissue targeted for treatment. For example, a protruding abnormal tissue target can be treated using a discharge electrode with a shape having a concave surface that can be positioned to partially surround the protrusion. Conversely, a curved inner surface of a body organ (e.g., the interior of a colon, bladder, or other hollow organ) can be accommodated by providing a discharge electrode shaped as a convex surface that can be positioned at a location where it follows the inner curvature of the surface.

[0247] The geometries of the multiple plasma generation elements, such as their multiple dimensions, multiple symmetries, and / or multiple relative positions, also affect the shape of the plasma plume. For example, increasing the lumen diameter and / or the ionized gas flow tends to result in higher power (resulting in more ionization) and a longer plasma plume. A greater electrode width (in a proximal-to-distal direction along the ionized gas flow) also tends to result in higher power. A thinner or lower-resistance dielectric barrier results in a lower breakdown voltage.

[0248] To monitor the multiple effects of modifying the multiple plasma generation parameters on the plasma generation itself, at least two general methods can be applied.

[0249] In the first method, the power delivered by an electrical power supply to the discharge electrode can be monitored. A "target" power level can be selected, for example, based on multiple experiments correlating multiple processing effects with multiple power levels and / or correlating multiple temperature levels with multiple power levels. If the power is found to deviate from the target level, multiple adjustments can be made until the target power level is reached again. It should be noted that this does not require adding additional multiple elements to the plasma delivery tip itself.

[0250] Additionally or alternatively, direct temperature monitoring can be performed, for example, by using a thermistor, a thermocouple, and / or a spectroscopic probe placed in a suitable location. For example, the probe can be placed inside the lumen of a plasma delivery tip and / or on a discharge electrode of a plasma delivery tip. Optionally, the temperature monitoring probe is brought near the site of plasma treatment as a separate tool inserted through the lumen for delivering the ionized gas and / or the discharge electrode. Optionally, the temperature monitoring probe is brought near the site of plasma treatment through an auxiliary channel, such as a working channel of an endoscope rather than the lumen for delivering the ionized gas and / or the discharge electrode. Spectroscopic monitoring can also be used to measure the multiple concentrations of active species in the plasma (based on their specific emission spectra). Optionally, this information is used to guide the adjustment of the multiple plasma generation parameters.

[0251] For simplicity, most of the examples described herein omit specific indications of the locations of the multiple sensing devices used for monitoring. However, it should be understood that any of them can be equipped with a thermal sensor and / or a spectroscopic sensor, such as generally described herein Figure 1H as described.

[0252] The multiple changes made in response to multiple deviations of the monitored power and / or temperature from multiple target levels vary depending on the particular embodiment. Multiple principles for making these changes are further discussed with respect to the multiple particular embodiments. It should be understood that these principles, even when described with respect to a particular embodiment, apply to other multiple embodiments sharing a related feature. These principles may be related to, for example, multiple effects on plasma generation to regulate multiple diameters, multiple lengths, multiple thicknesses, multiple relative distances, multiple relative orientations, multiple ionized gas flow velocities, and / or multiple applied voltages.

[0253] One aspect of some embodiments of the present invention relates to the construction of multiple plasma delivery tip elements for navigation and / or penetration of tissue by the plasma delivery tip.

[0254] In some embodiments, an electrical power conduit (e.g., a coaxial cable) interconnecting a discharge electrode to a high-voltage power source also serves as a steering control, e.g., to manipulate the orientation of the plasma delivery tip according to the tension applied to the electrical power conduit.

[0255] In some embodiments, an electrical power conduit (e.g., a coaxial cable) interconnecting a discharge electrode to a high-voltage power source also serves as a guidewire. For example, the electrical power conduit can be advanced from the plasma delivery tip to select during the advancement of the plasma probe at multiple different potentials, where the plasma delivery tip is part of the plasma probe.

[0256] In some embodiments, the shape of a discharge electrode facilitates the advancement of a plasma probe, where the plasma delivery tip is part of the plasma probe. For example, the discharge electrode is covered with a non-invasive tip (e.g., including the dielectric barrier layer), and the tip is shaped to facilitate guiding the advancement of the electrical power conduit when used as a guidewire. Alternatively, the discharge electrode is covered with a sharp tip (e.g., including the dielectric barrier layer), and the tip is adapted to penetrate tissue and / or multiple obstructions.

[0257] In some embodiments, a lumen for delivering ionized gas is beveled to a sharp tip, adapted to penetrate tissue and / or multiple obstructions.

[0258] One aspect of some embodiments of the present invention relates to various methods of constructing a rigid but small-diameter discharge electrode assembly. In some embodiments, a discharge electrode assembly is constructed based on a coaxial cable by stripping the outer insulation and flexible shield from a distal portion of the coaxial cable and then replacing the flexible shield with a stiffer shield (such as a metal tube), while leaving a distal portion of a central conductor of the coaxial cable unshielded. The unshielded portion of the central conductor is provided with the dielectric barrier material, optionally shaped to facilitate use of the discharge electrode assembly for navigating and / or penetrating tissue at a point. Optionally, outer insulation is provided to electrically insulate the stiffer shield.

[0259] One aspect of some embodiments of the present invention relates to multiple gas return channels of a plasma delivery tip.

[0260] When a plasma plume introduces gas into a body space, the gas volume and / or pressure may increase. In some embodiments, a plasma delivery tip is provided with multiple return channels configured to mitigate such accumulation (passive return of gas). In some embodiments, a connector is provided proximal to the gas return channels that allows attachment of a negative pressure source (suction) to assist and / or induce the return of the ionized gas.

[0261] In some embodiments, the multiple return channels are helical. This provides a potential advantage for cooling because the gas that has been heated by plasma generation cools slightly as it interacts with the environment. The returned gas can also absorb some heat from the plasma delivery tip. Returning along a helical path increases the surface area over which this heat exchange occurs, potentially increasing the efficacy of the returned gas as a coolant.

[0262] One aspect of some embodiments of the present invention relates to multiple sleeves for multiple plasma delivery tips that protect the plasma delivery tip as it travels through a working channel.

[0263] In some embodiments, the size of a plasma delivery tip is adapted to be delivered through a working channel of a device that may also optionally be used for a variety of other tools during the procedure. Thus, use of the plasma delivery tip includes advancing the plasma delivery tip distally through the working channel.

[0264] For multiple plasma delivery tips having multiple geometric arrangements of relatively complex (i.e., non-circular and / or consisting of multiple free ends), multiple distal features, protecting the plasma delivery tips with a sleeve is a potential advantage. However, using a sleeve can occupy working channel space, presenting a potential disadvantage. This results in the plasma delivery tip itself requiring a narrower design, potentially increasing the resistance to the flow of the ionized gas therethrough, and / or reducing the cross-sectional area of a plasma plume delivered by the plasma delivery tip.

[0265] However, a sleeve may have multiple important functional features related to the electrical function of a plasma delivery tip. In some embodiments, a provided sleeve includes a dielectric material. Adding the additional thickness of the dielectric material may prevent the voltage itself transmitted to the electrical conduit of the discharge electrode from causing a plasma discharge. The sleeve can also help prevent gas from seeping back into the working channel around the ionized gas supply tube, where it may contribute to the ectopic generation of plasma. It should be understood that any of the multiple embodiments described herein is optionally provided with a dielectric insulating sleeve that can extend partially or completely along a length of a high-voltage conductor for bringing voltage to a plasma delivery tip for generating plasma. Additionally, the sleeve can be sized to have an outer diameter that fills a lumen for delivering the plasma delivery tip to its operating position within a body cavity, thereby providing a seal to prevent the retrograde transport of plasma - further helping to prevent the occurrence of ectopic plasma discharges. In some embodiments, there is no such seal, and in fact, the ionized gas may flow proximally along the sleeve. In those embodiments, the sleeve is optionally designed to provide a dielectric thickness that prevents the voltage carried within the sleeve from causing ectopic plasma generation. Optionally, for another reason, the sleeve is specifically provided and / or thickened in multiple regions where electrical isolation is reduced. These regions can include, for example, multiple regions where the ground shield of a coaxial cable is weakened and / or not provided; for example, to reduce space usage to allow for multiple electrical connections, or for other purposes.

[0266] One aspect of some embodiments of the present invention relates to multiple plasma delivery tips including multiple plasma generation sites that operate together to provide an increased plasma treatment area.

[0267] More specifically, this aspect relates to multiple embodiments provided with multiple plasma generation sites, where the multiple plasma plumes generated by them are preferably directed to multiple positions in a region that are complementary to each other to complete coverage.

[0268] These features provide a solution to the problem of matching the plume size to the target size.

[0269] The problems arise in part because miniaturization reduces the size of a plasma delivery tip to a diameter of 2 to 20 mm (typically), suitable for use within a body cavity. For such intracavitary (e.g., endoscopic) procedures, it can be readily appreciated that a final target (e.g., a target including abnormal tissue such as a tumor and / or infected tissue) may be much larger than the size of the access path to it using a processing tool such as a plasma delivery tip.

[0270] The problems are also related to the practical issue that for any particular geometry of a plasma delivery tip, in practice the plasma may only be verified for use within a relatively narrow range of plasma generation parameters. In particular, the range can include a relatively narrow range of plasma plume sizes (e.g., diameters and / or cross-sectional shapes).

[0271] Outside this range, plasma generation may not occur reliably (or at all); or it may occur, but the generation of potentially therapeutic plasma species is unknown or insufficient. In general, simply scaling up a small plasma generation tip to a larger one results in such a large change in plasma generation characteristics that at some point it must be effectively re-verified as a new design. This type of scaling may not even be practical - e.g., because of access size limitations, and / or because the increased size increases the requirements for breakdown voltage levels (discharge electrode voltages) beyond reasonable and / or feasible ranges.

[0272] In some embodiments of the present invention, a plurality of plasma generation sites are provided, each plasma generation site being placed at a location where it generates plasma within a region of an air flow, while other plasma generation sites do not generate plasma therein, or at least do not generate a sufficient concentration of plasma therein.

[0273] The plurality of different plasma generation sites are distinguished at least by including a plurality of separate discharge electrodes. The plurality of electrodes can be electrically isolated from each other (e.g., each being driven by a separate power source), or (more simply), electrically interconnected by an electrical conduit that itself does not serve as a discharge electrode for generating plasma.

[0274] In some embodiments, the plurality of different plasma generation sites can also be distinguished by separating the ionized gas into a plurality of different flows. For example, a plurality of outlet holes can be provided from a gas delivery tube, each outlet hole being provided with its own discharge electrode. Additionally or alternatively, a plurality of ionized gas delivery tubes can be provided, either supplied with ionized gas separately (e.g., from a pressure source regulated separately at a proximal end of the supply tube), or connected together to a main ionized gas delivery tube to form a manifold.

[0275] The plurality can also be composite; for example, one of the plurality of outlet holes itself can be provided with a plurality of discharge electrodes, and / or one of the plurality of gas supply pipes itself can be provided with a plurality of outlet holes.

[0276] In some embodiments, each plasma generation site generates plasma according to a plurality of substantially identical parameters, such as the same outlet hole size, the same rate at which gas flows therethrough, the same discharge electrode geometry, and / or the same discharge voltage.

[0277] Optionally, the plurality of plasma generation sites are also provided with the same basic support structure design: for example, each site is located at the distal end of a tube longitudinally extending from a distal end of a delivery sleeve, or each site is located in a transverse hole of such a tube.

[0278] In some embodiments, a plurality of sites having a plurality of substantially identical parameters affecting plasma generation (such as gas flow, outlet hole size / shape, electrode design, and / or discharge voltage) are embedded in a plurality of different support structures. For example, one or more outlets can be oriented to direct a plume along a longitudinal axis of a distal portion of the plasma delivery tube, while one or more other outlets can direct the plume at an angle to the longitudinal axis and / or perpendicular to the longitudinal axis.

[0279] The plurality of plasma generation sites can be pre-arranged such that they produce a pattern of a plurality of individual plasma plumes that are complementary to each other to produce a combined plume, and the combined plume is shaped to ensure coverage of a specific area. The shape of the combined plume itself can be large enough to cover the "total" target area, or its shape can make plasma plume scanning easier and / or more reliable. For example, the combined plume can cover a linear area, and the linear area can be scanned by a plurality of movements perpendicular to the linear area (such as by bending of a plasma delivery tube) to obtain area coverage. The combined plume can be formed as a ring circumferentially surrounding an arrangement of a plurality of outlets, allowing it to be longitudinally advanced through a substantially tubular lumen, such as a lumen of an intestine.

[0280] The plurality of individual plumes of the combined plume are optionally combined by using a scanning motion. For example, a plurality of laterally projected plasma plumes can be rotated about a longitudinal axis to produce an annular plasma coverage area. In some embodiments, a plurality of bending movements of a plasma delivery tube cause a plurality of plumes of a grid of a plurality of plumes arranged substantially in parallel to cross into each other's previous coverage areas, thereby producing a combined coverage area.

[0281] One aspect of some embodiments of the present invention relates to a plurality of plasma delivery tips including a plurality of plasma generation sites, the plurality of plasma generation sites being delivered in a first configuration and then rearranged into a new configuration that allows them to operate together to provide an increased plasma treatment area.

[0282] In some embodiments, the plurality of plasma generation sites are rearranged after deployment into a shape suitable for providing target coverage. The rearrangement can help overcome the mismatch between the via diameter and the target size. In some embodiments, the plurality of plasma generation sites are individually mounted on a plurality of tubes that are advanced from the confines of a sleeve and / or a working channel to assume an open shape capable of delivering a combined plasma plume that may cover a wider area than the area covered by operating the plurality of identical plasma generation sites in a more compact delivery configuration. In some embodiments, the open shape is accomplished by increasing the spacing between the plurality of plasma generation sites. In some embodiments, the open shape is substantially linear; for example, a linear shape rearranged from a compact structure that exists when the plurality of sites are confined within a substantially circular lumen of a sleeve.

[0283] Optionally, multiple spacing increases are achieved, for example, by mounting each plasma delivery site at the end of a tube that slightly bends when released from the sleeve and / or channel confinement, thereby achieving a more dispersed configuration. Optionally, the plurality of tubes themselves are amenable to being bent into the deployed configuration. Optionally, a flexible truss is used that expands when released from confinement to help position the plurality of tubes in their deployed configuration.

[0284] One aspect of some embodiments of the present invention relates to modifying the plasma plume shape to fit the target geometry.

[0285] Where the plurality of plasma plumes exit a delivery tube orifice, the plurality of plasma plumes made of a jet gas may tend to assume a pencil-shaped or other shape, such as an expanding funnel. This shape is the result of many factors, such as: multiple ionized gas parameters, multiple ionized gas flow parameters, multiple electrical parameters for generating the initial ionized species in the plasma, multiple geometric parameters such as electrode and plasma exit orifice shape, and multiple electrical interactions of the gas flow and / or the plasma plume with its environment. Due to its velocity, a jet gas plume has some potential advantages in projecting the plasma to sites beyond the site where it is generated.

[0286] However, there is no specific requirement to generate plasma in a jet of ionized gas. In some embodiments, for example, optionally a generally static atmosphere of ionized gas (e.g., which can be established within a hollow body organ such as a bladder or an intestine) is generated. Then, the plasma plume shape may be governed by the shape of the discharge electrode - the discharge electrode itself does not necessarily lie within the lumen of the tube for delivering the gas. In this case, the discharge electrode itself can be positioned directly adjacent to and operate on a surface targeted for plasma treatment. For example, the discharge electrode can be curved to match the curvature of the surface. The discharge electrode can be scanned over the surface, for example, by rotation and / or by multiple bending motions of a tube for delivering the discharge electrode.

[0287] In some embodiments, plasma generation is carried out in a state where an ionized gas flow and a discharge electrode are positioned between the two extreme states just described. For example, an ionized gas jet may be disrupted and / or redirected due to the presence of multiple surfaces in the environment, such as when the target surface itself is located distally from the outer orifice from which the ionized gas is emitted. The ambient gas can be completely or partially replaced with the ionized gas.

[0288] Regardless of whether the replacement is complete, the plasma plume shape may still be affected by the gas flow. In some embodiments, multiple discharge electrodes are configured to be positioned within the redirected (e.g., laterally directed) ionized gas flow, outside of the tube for delivering the gas. The shape of the discharge electrode itself optionally contributes to the redirection of the ionized gas, for example, having multiple baffles, and / or only by acting as a barrier to its own flow. Optionally, a discharge electrode can be manipulated while the gas flow remains substantially in place. In some embodiments, a discharge electrode is configured to extend laterally from a longitudinal axis of the same tube for delivering the ionized gas. When close enough to a target surface, the ionized gas flow turns laterally. Rotating the discharge electrode sweeps it across multiple different circumferential portions of the laterally flowing ionized gas. Since plasma is generated where the ionized gas intersects the electrode, the sweeping motion of the electrode also generates an increased plasma coverage area. Similarly, optionally a shaped electrode can be used to fit a particular target surface shape; for example, the electrode can be curved so that a convex surface of the electrode rests against a complementary concave target surface.

[0289] In addition, there is no particular requirement to generate plasma from a circulating flow of singly ionized gas. In some embodiments, plasma is generated within a flow of ionized gas shaped by a non-circular exit aperture, such as an elliptical or slit-shaped exit aperture. In particular, multiple exit apertures having a major axis and a minor axis (e.g., the major axis is at least twice as long as the minor axis) provide a potential advantage by spreading the plasma plume into a more linear shape. The more linear shape can then be scanned in a direction perpendicular to its major axis to produce a larger scanned area with each sweep. Additionally, multiple sequential sweeps offset in a direction parallel to its major axis may be easier to control - for example, there is a lower tendency to leave multiple coverage gaps between adjacent sweeps.

[0290] One aspect of some embodiments of the present invention relates to multiple plasma delivery tips configured to distribute plasma to multiple surfaces by using "scanning" multiple motions. In some embodiments, the scanning motion includes rotation of an exit aperture of the tip around a circular path. In some embodiments, the orientation of the exit aperture is selectable and / or dynamically controllable, thereby providing multiple additional options for generating plasma coverage of a target surface.

[0291] In some embodiments, the supply is for "scanning" one or more plasma plumes to cover a larger area than the cross-section provided by the multiple plumes themselves. This also potentially helps to ensure that a target surface receives sufficient plasma coverage.

[0292] The scanning can be performed, for example, by using control of the bending and / or advancement of a gas supply conduit, a sleeve of the gas supply conduit, and / or a working channel. Additionally or alternatively, in some embodiments, the scanning is performed by rotating a gas supply conduit, a sleeve of the gas supply conduit, and / or a working channel.

[0293] It should be noted that any one of the bending, advancement, and / or rotation is optionally dynamic during scanning (e.g., multiple variations of the bending, advancement, and / or rotation themselves complete the scanning), and / or is used to set a configuration of the plasma delivery tip that controls how multiple plasma plumes are directed when using another degree of freedom of motion.

[0294] Adding multiple plasma plumes, controlling the direction of these plasma plumes, and / or scanning these plasma plumes by moving them over a target area are all methods that can potentially overcome the multiple limitations imposed by such practical considerations. The same selected multiple plasma generation parameters can be replicated at multiple exit apertures to similarly produce a plasma plume at each, and then all of these plasma plumes can be combined to deliver plasma to a target area.

[0295] One aspect of some embodiments of the present invention relates to a plurality of plasma delivery tips that incorporate membership in two or more of a group of plasma delivery tips defined by the following plurality of features:

[0296] · A plurality of tips that allow reshaping to adjust a plurality of parameters of plasma generation - for example, through a plurality of variations in the dielectric barrier layer thickness, discharge electrode shape and / or position, and / or plasma exit aperture size. The tip reshaping can be controlled by an actuation control member (either directly or by removing a limiting element), or the tip can be automatically reshaped, for example, as a function of temperature.

[0297] · A plurality of tips that generate a plasma plume that can be actively redirected remotely when the tip is located within a body cavity. For example, the redirection can include rotation of a plurality of elements relative to an introduction lumen used with the tip and / or bending of a plurality of elements that generate the plasma plume.

[0298] · A plurality of tips that include a plurality of plasma generation sites; for example, a plurality of sites defined by a corresponding plurality of electrodes and / or a plurality of ionizing gas supply tubes.

[0299] Before explaining in detail at least one embodiment of the present invention, it should be understood that the present invention is not necessarily limited in its application to the construction and arrangement of the components and / or methods described in the following description and / or illustrated in the plurality of figures. The plurality of features described in the present disclosure, including the features of the present invention, can have other embodiments or can be practiced or carried out in various ways.

[0300] Plasma processing device

[0301] Now refer to Figure 1A , which schematically shows a plasma processing device 55 according to some embodiments of the present invention.

[0302] In some embodiments, the plasma processing device 55 includes a high-voltage power controller 60 and an ionizing gas supplier 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 other electrical conduit having a controlled impedance and shielded along its length). The ionizing gas supplier 61 supplies an ionizing gas to the plasma probe assembly 62 through a pipe 72. The supplied gas 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 pipe 72 are integrated into a single cable unit connected to the plasma probe assembly 62. Optionally, the high-voltage power controller 60 and the ionizing gas supplier 61 are integrally housed.

[0303] The plasma probe assembly 62 optionally includes a handle 80. The handle 80 is optionally provided with controls 81, 82 for controlling the actuation of the probe catheter 73 and / or the plasma delivery tip 66, for controlling multiple functions of the power controller 60, and / or for controlling the delivery of the ionized gas from the gas supplier 61. Optionally, the plasma probe assembly 62 physically integrates multiple power functions and multiple gas delivery functions into the probe catheter without using a dedicated handle. In some embodiments, the probe catheter 73 includes a lumen for delivering the ionized gas and a high voltage (e.g., a continuation of the cable 71 and the conduit 72). In some embodiments, the probe catheter includes multiple lumens, such as a lumen attached to the gas supplier 61 for delivering the ionized gas, and optionally a lumen for purging (removing) the ionized gas under suction. In some embodiments, any one or more of the multiple lumens of the probe catheter 73 are optionally used as a working channel by inserting a tool (e.g., a tool described with respect to Figures 10A to 10C ). In some embodiments, the handle 80 includes one or more ports 83 for introducing such tools into a lumen of the probe catheter 73.

[0304] In some embodiments of the present invention, the probe catheter 73 and the plasma delivery tip 66 are sized and configured (e.g., a safety configuration) for delivering cold plasma to an in-vivo location.

[0305] The multiple embodiments described herein relate to various different configurations of the plasma delivery tip 66. In some embodiments, a plasma delivery tip 66 includes a lumen configured to deliver the ionized gas; and a discharge electrode located within the ionized gas flow. In addition, the discharge electrode is configured to receive a high voltage, is insulated from direct contact with the ionized gas flow through a dielectric barrier layer, and is otherwise insulated from the environment as needed through an insulating sheath layer (e.g., on multiple sides away from the ionized gas flow if any). Herein, several different embodiments of each of these elements are described, many of which have multiple additional features, such as controllable multiple dimensions, multiple shapes, multiple thermal properties, and / or multiple electrical properties. Generally, the multiple features and multiple elements described herein in connection with multiple different embodiments should be understood to be optionally provided together as long as they are mutually compatible.

[0306] Two general categories of plasma delivery tips 66 include multiple tips configured with a discharge electrode substantially surrounding the ionized gas flow (e.g., described with respect to Figures 1B to 1F Figures 2A to 5D) and multiple tips configured with the ionized gas flow substantially surrounding the discharge electrode (e.g., described with respect to Figures 6A to 11D(as described). At least in each category, it should be understood that, among the plurality of embodiments, a plurality of first elements whose operation described in one of the plurality of embodiments does not essentially depend on the specific design of a second element can optionally be combined with a plurality of second element designs described with respect to another of the plurality of embodiments.

[0307] For example, a plurality of different ways of changing the shape of a discharge electrode to adapt to a varying diameter of a dielectric barrier layer are described herein. A plurality of discharge electrodes of a certain type of shape change can be freely combined with a plurality of dielectric barrier layers of different types of shape change, as long as the discharge electrode itself is not part of the shape change mechanism of the dielectric barrier layer. Even in the case where two elements interact (e.g., the discharge electrode contracts to compress the dielectric barrier), more than one way of implementing the interaction substantially as described can also be disclosed herein. It should be understood that a plurality of elements can be easily combined between a plurality of embodiments in which a plurality of mechanisms remain substantially the same.

[0308] Another example of interchangeability between a plurality of embodiments includes the construction of the insulating sheath layer. In some embodiments herein, a plurality of insulating sheath layers are described as including a tube or a ring, having a plurality of other optional features, such as being optionally deformed actively or passively in the radial and / or longitudinal directions, e.g., by the operation of a control member or by the movement of a plurality of other elements such as the discharge electrode and / or the dielectric barrier layer; and / or having a hollow portion sized to accommodate an electrode and allow changing the shape of the electrode. Additionally, in some embodiments, a plasma delivery tip is configured with a plurality of channels formed at least partially by the insulating sheath layer, the plurality of channels being for removing ionized gas and / or plasma after delivery (e.g., having an exhaust channel that also extends along the probe conduit 73). It should be understood that these features of the plurality of insulating sheath layer constructions can be interchangeably separated and combined between a plurality of embodiments - with each other, and with a plurality of other different constructions of a plurality of other elements such as a plurality of electrodes and / or the plurality of constructions of the dielectric barrier layer - as long as these combinations are mutually compatible.

[0309] Additionally or alternatively, a plurality of embodiments not separately described as being provided with a dielectric sleeve can still optionally be provided with one. Further, if mentioned separately, the sleeve can be provided as a spaced protection type and / or tip protection type sleeve, which acts as an attachment between a plasma delivery tip and a working channel through which the plasma delivery tip is advanced. Additionally, the sleeve can be a sealed type sleeve that prevents the backflow of ionized gas, or alternatively a sleeve that has itself as part of a retrograde gas conduit, e.g., as described with respect to Figures 5A to 5D as described.

[0310] In some embodiments, one or more of these elements (or another element that plays a role in plasma generation, such as an electrical power delivery conduit or a portion thereof) are configured to perform one or more functions for a plurality of device capabilities other than plasma generation. For example, an electrode, wire, and / or cable is configured to induce a plurality of steering movements of the device (e.g., Figure 3A , 14B to 14C) to temporarily reconfigure the device to assist in device advancement (e.g., Figure 3B ), and / or act as a guide wire (e.g., Figure 9 ). Additionally or alternatively, multiple specific features of multiple structural elements are described, including, for example, multiple beveled tips ( Figure 4 , 6D ), multiple reinforcement members ( Figure 4 ), and / or multiple positioning supports ( Figures 6C to 6F , 15A to 15C). It should be understood that these features can be separated and combined interchangeably among multiple embodiments - with each other, and with other multiple different configurations of other multiple elements such as multiple electrodes, the dielectric barrier layer, and / or the insulating sheath layer - as long as these combinations are mutually compatible.

[0311] Figure 1A A plasma probe assembly 62 is shown in a "stand alone" configuration, e.g., a configuration in which it can itself be used as a navigable catheter to reach an in - vivo target. However, it should be understood that in some embodiments, a plasma probe assembly 62 can optionally be used with another device; for example, by passing it through the working channel of an endoscope, or by inserting it into the lumen of a separate catheter. The plasma probe assembly 62 is shown as including a flexible probe catheter 73. However, it should be understood that the probe catheter 73 can optionally be rigid, and can optionally be straight or curved. The probe catheter 73 can optionally have any suitable length to reach its target.

[0312] Some embodiments of the present invention are described as including a sheath tube 101 having a lumen, and multiple elements of a plasma delivery tip are advanced in the lumen. Optionally, the sheath is part of the probe catheter 73. Optionally, the sheath is provided as the lumen of a device into which the plasma probe assembly is inserted, such as the working channel of an endoscope or a separately provided catheter. The shown and / or described embodiments without a sheath can optionally be provided and / or operated with a sheath. Conversely, embodiments described with a sheath can optionally be provided and / or operated "sheathless", although certain features that specifically rely on the sheath (such as using a portion of its lumen space as a gas and / or plasma return path) may not be available subsequently.

[0313] These comments regarding multiple combinable elements and / or multiple element features should also be understood as multiple teaching principles summarized by the multiple examples described herein; using the multiple teachings herein, one of ordinary skill in the art can identify multiple combinations of multiple elements and / or multiple element features that are within the scope of these descriptions through these principles. These comments and principles should not be construed as teachings by any so-called omissions or mutual exclusions of multiple elements and / or multiple element features.

[0314] Multiple adjustable geometric plasma delivery tips

[0315] Now refer to Figure 1B , which schematically shows a plasma delivery tip 66 configured with an adjustable lumen diameter according to some embodiments of the present invention.

[0316] In some embodiments of the present invention, multiple examples of a plasma delivery tip 66 include a generally tubular assembly that is about 0.5 to 5 cm long (e.g., about 1.5 cm long) and about 1.5 to 6 mm in diameter (e.g., about 3 mm in diameter) in a proximal to distal direction. The tubular assembly optionally includes multiple layers - an inner dielectric barrier layer 103 and an outer insulating sheath layer 102.

[0317] The circumferential interior of the dielectric barrier layer 103 is a lumen through which an air flow 8 passes when the plasma delivery tip 66 operates. A discharge electrode 106 is generally disposed around a circumferential portion of the dielectric barrier layer 103. Electrical power of a high alternating voltage (e.g., 500 V to 2000 V) is supplied to the discharge electrode 106 to ionize the air flow 8 into a plasma. The frequency of the alternating voltage is selected, for example, from radio frequency (RF) to multiple microwave frequencies. In some embodiments, the supply is provided through an electrical conduit 105. Optionally, the electrical conduit 105 includes a coaxial cable, and an outer conductor of the coaxial cable isolates the voltage supplied on the central conductor until it reaches the unshielded discharge electrode 106. Herein, it should be understood that multiple embodiments described as including a coaxial cable can optionally be implemented by replacing and / or reinforcing the coaxial cable with another electrical conduit configured to deliver a voltage to a discharge electrode along a shielded and / or insulated range to prevent accidental multiple power losses and / or discharges along its length. A coaxial cable provides a potential advantage for multiple thin plasma delivery probes because it uses optionally relatively thin multiple surrounding material layers, for example, a coaxial cable with an outer diameter of 1.1 mm can be provided, and the coaxial cable can maintain at least a 1000 V RAMS isolation from the environment.

[0318] The insulating sheath layer 102 is configured to keep the discharge electrode 106 otherwise sufficiently electrically isolated (even, for example, in a fluid environment) such that at least the majority (e.g., 90% or more) of the actual power transmitted from the electrode 106 is directed into the gas stream 8.

[0319] Optionally, the electrode 106 is encapsulated within a space 107 defined by the insulating sheath layer 102. The electrode 106 can be tightly encapsulated (e.g., with the material of the sheath layer 102 cast around it). Optionally, the electrode 106 is loosely encapsulated to allow for multiple movements of the electrode 106 to accommodate multiple variations in the geometry of the layers 102, 103.

[0320] In some embodiments, a plasma delivery tip 66 is delivered through a passageway within the lumen of a sheath tube 101, such as a catheter sheath and / or an endoscope working channel.

[0321] Optionally, the insulating sheath layer 102 and the dielectric barrier layer 103 are made of any suitable non-conductive material; for example, ceramics, Pyrex TM , quartz, and / or a biocompatible plastic and / or rubber material. Multiple examples include polyetheretherketone (PEEK), silicone rubber, and polytetrafluoroethylene (PTFE). In some embodiments, the two layers are joined but separate, optionally including multiple different materials having multiple different electrical and / or mechanical properties. The two layers 102, 103 are optionally fabricated as a single unit and optionally made of a single material, although this may impose multiple limitations on the selection of multiple parameters such as multiple electrical insulation properties and / or relative degrees of freedom of movement.

[0322] Given that in some embodiments the plasma delivery tip 66 is relatively small in size (e.g., about 3 mm in diameter and about 5 mm in axial length), it can be understood how the structure including the insulating sheath layer 102 and the dielectric barrier layer 103 can be constructed to have a thinness and flexibility that enables it to undergo a relatively large deformation by applying multiple relatively small forces.

[0323] Figures 1B to 1D Embodiments are shown that use multiple altered relative longitudinal forces applied proximally to the plasma delivery tip 66 to control either a lumen width of the dielectric barrier layer 103, a wall thickness of the dielectric barrier layer 103, or both. According to the construction, either or both of longitudinal compression and tension can reduce the lumen width. According to the Poisson effect, longitudinal compression can reduce the lumen width, where a material tends to expand in multiple directions perpendicular to the direction of compression. Inward expansion results in a reduction in the lumen diameter. According to a tendency for a material to contract in multiple directions transverse to the direction of tension, longitudinal tension can reduce the lumen width. For example, regardingFigures 1E to 1G , describes multiple examples of multiple devices that use other multiple operating principles to change one or both of these features. Multiple variations in the dielectric barrier layer thickness can be, for example, a ratio (thin divided by thick) as low as about 0.9, 0.75, 0.5, 0.25, or other ratios. Multiple variations in the gas lumen diameter (e.g., at a narrowest point, or at a widest point) are optionally a ratio (narrow divided by wide) as low as about 0.9, 0.75, 0.5, 0.25, or other ratios.

[0324] In Figure 1B each of the multiple figures of Figure 1C , the dielectric barrier layer 103 and the sheath layer are optionally attached to each other at their distal ends (e.g., at the attachment location 125; and, for example, attached by an adhesive, heat welding, and / or multiple pins), and / or mechanically constrained (e.g., by multiple flanges 109 as shown in

[0325] to prevent them from completely sliding past each other. However, along their bodies, the two layers 102, 103 can slide freely relative to each other.

[0326] Layer 102 is elastically deformable. The distal-directed force thereon is optionally transferred from a relatively inelastic control member 104, which includes, for example, a tube (e.g., as shown), a cable, and / or other elements that longitudinally extend through the sheath 101 to interconnect a control operated by a user and layer 102.

[0327] Layer 103 is optionally elastic, but long enough such that its multiple longitudinal elastic deformations are widely distributed and can be negligible over the length where layer 103 is encapsulated by layer 102. Optionally, layer 103 is also attached to its own control member (e.g., a control member 108 as shown in Figure 1C .

[0328] In Figure 1BIn the top view described above, a relatively high differential tension is applied by pulling proximally on layer 103 and pushing distally on layer 102. Since layer 102 is longitudinally compressed (e.g., compressed to a dimension indicated by arrow 132), a portion of its volume is displaced inwards. Layer 103 is compliant enough to deform inwards in turn, thereby reducing the diameter of the lumen of layer 103 (e.g., reduced to a dimension indicated by arrow 131). As a result, there may be a slight change in the wall thickness of layer 103, but the main effect in the configuration shown is on the lumen diameter. Optionally, a narrow lumen is selected to regulate a plasma jet, e.g., to increase its exit velocity and potentially increase its length. Although the increased resistance of a narrow orifice may potentially reduce the net flow through the device (reducing some cooling effect), the increased flow velocity may still reduce heat transfer to the device itself.

[0329] In Figure 1B In the bottom view described above, the differential tension has been fully relaxed. This allows each of layers 102 and 103 to expand to its natural length (e.g., as shown by arrow 134) and diameter in at least a plurality of portions not constrained by the protective sheath 101. Accordingly, the lumen of layer 103 also widens (e.g., as shown by arrow 133). Optionally, a wide lumen is selected to create a larger internal working volume, thereby potentially increasing the amount of ionization power that the device can receive without causing an unacceptable level of local heating.

[0330] In some embodiments, the plasma delivery tip 66 is primarily designed for a first delivery mode configured to be small enough to fit within a selected dimension of the lumen of a protective sheath 101, and then a second operating mode that expands to provide a plasma with targeted temperature, electrical, and / or plasma generation characteristics. In some embodiments, a plasma delivery tip 66 is designed to allow for variations in temperature, electrical, and / or plasma generation characteristics during plasma generation.

[0331] Now refer to Figure 1C , which schematically depicts a plasma delivery tip 66 configured with a tension-adjustable lumen wall thickness in accordance with some embodiments of the present invention.

[0332] Figure 1C The device described above is specifically configured to produce multiple variations in the wall width of layer 103. Layer 102 is relatively inelastic, while layer 103 is relatively elastic (and optionally shorter than that shown in Figure 1B ), such that when layer 103 receives an increased proximal force (top figure), it is pulled thinner (as shown by arrow 109). Optionally, layer 103 is configured to have a relaxed and unconstrained diameter slightly larger than the inner diameter of layer 102 to prevent the lumen of layer 103 from collapsing inwards.

[0333] As the relative tension decreases (middle and lower figures), layer 103 gradually thickens accordingly (e.g., as indicated by arrow 136). This thickening tends to increase the resistance, impedance, and / or dielectric strength of layer 103, correspondingly increasing the breakdown voltage and / or reducing the ionization power of the voltage delivered to discharge electrode 106.

[0334] Now refer to Figure 1D , which schematically shows a plasma delivery tip 66 configured with a co - adjustable lumen wall thickness and lumen diameter according to some embodiments of the present invention.

[0335] In this embodiment, in other aspects similar to the Figure 1C embodiment, layer 102 is elastically deformable enough to also substantially deform (e.g., under the multiple longitudinal forces that modify the wall thickness of layer 103). Arrows 139 and 137 (upper figure) represent the longitudinal compression and lumen contraction of layer 102 as the multiple longitudinal tensile forces increase, relative to the middle figure. Arrow 138 (upper figure) represents the thinning of the wall of layer 103 relative to the middle figure.

[0336] Arrows 140 and 141 (lower figure) represent the longitudinal elongation and lumen widening of layer 102 (when longitudinally relaxed) relative to the middle figure. Arrow 138 (lower figure) represents the thickening of the wall of layer 103 relative to the middle figure as the multiple longitudinal forces relax.

[0337] Regarding each of the Figures 1B to 1D figures, it should be understood that the multiple layer configurations assuming relatively relaxed or increasing multiple longitudinal forces are optionally offset and / or inverted. For example, in each case, the top figure is optionally the "relaxed" longitudinal force diagram, and the bottom figure optionally has the maximum longitudinal force applied.

[0338] In some embodiments, multiple radial forces replace and / or supplement the multiple longitudinally applied forces to produce multiple variations in layers 102, 103. For example, as shown in the lower figure of Figure 1B and / or 1D, the retraction of a plasma delivery tip 66 into the sheath 101 optionally causes the lumen diameter to narrow due to compression within the sheath 101.

[0339] Now refer to Figure 1E , which schematically shows a plasma delivery tip 66 configured with a telescopically adjustable lumen wall thickness and lumen diameter according to some embodiments of the present invention.

[0340] In some embodiments, the lumen diameter and wall thickness of a dielectric barrier layer 103 are changed by using an arrangement of multiple nested telescopic tubes 103A, 103B, 103C. In a fully folded configuration (upper figure), each tube pair contributes to the impedance of the dielectric barrier that separates the lumen of layer 103 from the discharge electrode 106. In a fully extended configuration (lower figure), fewer tubes from the dielectric barrier are present (e.g., only one of them). Similarly, the lumen of layer 103 has a larger diameter at its most distal part in the extended configuration.

[0341] Optionally, the transition between the folded and extended configurations is actuated by a longitudinal movement of the electrical conduit 105, e.g., a distal movement, to move the telescopic tubes 103A, 103B, 103C into the extended configuration. Optionally, one or more of the tubes 103A, 103B, 103C have a thickness that varies along their length (i.e., from thinner to thicker), allowing for a more continuous variation of the dielectric barrier impedance.

[0342] Now refer to Figure 1F , which schematically shows a plasma delivery tip 66 configured with a distortable adjustable lumen diameter according to some embodiments of the present invention.

[0343] In some embodiments, a dielectric barrier layer 103D includes a material (e.g., a polymeric rubber) that has sufficient flexibility to allow its two ends to rotate relative to each other. The rotation causes layer 103D to distort, reducing its lumen diameter.

[0344] In some embodiments, the rotation is caused by the rotation of a control tube 108 connected to a proximal end of layer 103D. The control tube 108 itself is optionally rotated from a control member located at a proximal end of the device. A distal end of layer 103 is anchored, for example, by attachment to a sheath layer 102, which in turn is optionally fixed to a tube 104. Optionally, layer 102 is flexible enough to contract under the forces exerted by the distortion of layer 103D while still being rigid enough to resist distortion itself. Tubes 104 and 108 are relatively rigid, such that the deformations are concentrated within layers 102, 103D.

[0345] Now refer to Figure 1G , which schematically shows a plasma delivery tip 66 configured with a distortable adjustable lumen diameter according to some embodiments of the present invention.

[0346] In Figure 1GIn multiple embodiments of the type described, the dielectric barrier layer 103E is formed by a helically wound sheet or strip of insulating material. The tightness of the multiple windings is controlled by the operation of a control member. For example, a control line 121 is anchored at an anchor 120A to a first position of the layer 103E and is slidably anchored at an anchor 120B to a second position of the layer 103E. Tightening the line 121 reduces the distance between the anchors 120A, 102B, increases the winding tightness and reduces the diameter of the lumen of the layer 103E. Optionally, the tension applied to the electrical conduit 105 itself controls the winding.

[0347] Several windings are as Figure 1G shown. Optionally, a single winding is provided - i.e., a long sheet that is wound into a tube.

[0348] The sheath 101 is suppressed in Figure 1G but is understood to be provided, for example, as Figures 1B to 1F shown. In this case, the insulating sheath layer 102 is provided as a hollow ring, the material of which has sufficient elasticity to contract or expand to maintain a mating relationship with the layer 103E when the layer 103E contracts or expands.

[0349] In some embodiments, an optional hollow 107 of the layer 102 encapsulates the electrode 106. The electrode 106 is optionally configured to accommodate multiple variations in the diameter of the layer 103E. For example, in some embodiments, the electrode 106 includes a superelastic metal of a helical shape that expands or contracts (unwinds / winds as needed) to accommodate multiple variations in the diameter of the layer 103E. For example, multiple other shape-changing electrode configurations are described with respect to Figures 2A to 2H In general, multiple shape-changing electrode configurations of at least Figures 2A to 2G are interchangeably provided to Figures 1B to 1G multiple embodiments of lumen changes and / or wall thickness changes to passively accommodate multiple variations in the lumen and / or wall thickness, and / or to actively control the electrode geometry. In some embodiments, the proximal-to-distal extent of an electrode changes at a ratio (short divided by long) as low as about 0.9, 0.75, 0.5, 0.25 or other ratios.

[0350] It should be understood that Figures 1B to 1GMultiple examples are provided that represent a greater range of possible embodiments. In particular, embodiments of the present invention include multiple devices that can widen and / or narrow the lumen width of the dielectric barrier layer 103, and / or thin and / or thicken the wall of the dielectric barrier layer 103; for example, by longitudinal compression, longitudinal stretching, circumferential compression, circumferential stretching, inflation / deflation, and / or rotation. Control to produce these effects is optionally applied by multiple self-actuating (e.g., self-expanding) properties of a material, by pressure actuation, and / or by multiple electrical signals (e.g., electrical heating of a shape memory metal such as nitinol to induce bending) on, for example, multiple wires or multiple tubes.

[0351] In some embodiments of the present invention, one potential advantage is the achievement of electrical (isolation) and mechanical (shape change) functions through the combined use of the dielectric barrier layer 103 and the sheath layer 102. The simplicity of their construction and mechanical operation potentially helps to keep the device diameter small (e.g., 5 mm or less), while providing sufficient adjustability to match the plasma production capacity of the plasma delivery tip 66 with the multiple thermal limitations of cold plasma delivery for medical safety.

[0352] Now refer to Figure 1H , which schematically shows in cross-section multiple different thermal measurement device configurations for use with a plasma delivery tip 66 according to some embodiments of the present invention.

[0353] Any of the embodiments of the plurality of plasma delivery tips 66 of the present invention, such as those described herein and / or shown in other figures herein, are optionally provided with one or more sensors. Sensors 151, 152, 153 (optionally implemented, for example, as a plurality of thermocouple devices or a plurality of infrared temperature sensors) represent a plurality of sensors placed at a plurality of different exemplary locations: wall-embedded sensor 151 (within a wall facing the plasma delivery tip 66), wall-embedded sensor 154 (external to the wall facing the plasma delivery tip 66), lumen-located sensor 152 (within the plasma delivery tip lumen 22), and external-located sensor 153. Sensor 153A represents a sensor located separately from the plasma delivery tip 66, for example, by a separate probe 66B such as a catheter. One or more sensors are optionally provided at any combination of these locations, or at another location. Any of sensors 151, 152, 153, 154 optionally includes, for example: a temperature sensor, an electrode, a sensing optical fiber (collecting, for example, plasma spectral data), or another sensor; for example, a sensor configured to detect the presence and / or concentration of a specific ionized species (e.g., reactive oxygen and / or nitrogen species). Optionally, in some embodiments, a circuit element for plasma generation (e.g., the discharge electrode) also serves as a sensing element. Sensing optionally includes sensing multiple changes in multiple circuit characteristics when the electrode changes shape with temperature (e.g., for embodiments including a shape memory alloy such as nitinol), and / or sensing multiple changes in an electrical property such as resistivity with temperature. Sensing optionally includes impedance measurement, for example, to detect tissue contact and / or proximity.

[0354] The temperature sensing information is optionally provided to an operator and / or a controller for use in a feedback regarding the current temperature of the plasma delivery tip 66 and / or the plasma generated by the plasma delivery tip 66. For example, the temperature sensing information is optionally returned to the high-voltage power controller 60 (e.g., via cable 71). Optionally, the power delivery is adjusted and / or turned on / off according to the sensed temperature conditions. Optionally, the temperature sensing information is returned to the airflow control unit, which adjusts the airflow and pressure according to the sensed temperature (e.g., increasing pressure / flow to lower the temperature).

[0355] Optionally, the temperature sensing information is used to provide feedback that guides the automatic adjustment of multiple characteristics (such as multiple geometric and / or electrical characteristics) of the plasma delivery tip 66; for example, according to any of the multiple parameter adjustment methods and / or multiple mechanisms described herein. In some embodiments, a shape memory alloy is used to provide a plasma delivery tip 66 with multiple self-regulating characteristics. For example, when a discharge electrode heats up, it is optionally configured to change to a shape that is less efficient in delivering thermally generated power. This is a potential advantage for safety.

[0356] Additionally or alternatively, an operator can optionally adjust multiple parameters of plasma delivery based on sensed information, such as: sensed temperature (e.g., via a thermocouple) to keep a temperature within multiple allowed limits; and / or sensed contact and / or distance of a target (e.g., via an electrode) to determine when plasma generation should be performed.

[0357] Spectral sensing data can be used to detect the generation of multiple spectral lines and / or to detect the ratios of spectral outputs at multiple different wavelengths. This is optionally used to characterize plasma generation. Multiple adjustments can be made to the plasma generation to achieve a target spectral profile.

[0358] In some embodiments, sensors 152, 153 are positioned within the plasma stream when the plasma stream exits the lumen 22 (sensor 152) or after it exits the lumen 22 (sensor 153). Optionally, a sensor 152, 153 is variably positioned, for example, by advancing or retracting cables 152A, 153A that connect them to a measurement recorder located proximal to the plasma delivery tip 66 (e.g., positioned outside the body into which the plasma delivery tip 66 is inserted).

[0359] Sensors 152, 153 optionally include multiple temperature sensors placed where they measure the plasma temperature by direct thermal contact. Optionally, thermal sensing (e.g., IR-based thermal sensing) is performed from outside the plasma stream, for example, using sensors 151, 154 that include a thermocouple embedded in the wall of the plasma delivery tip 66 (and transmit measurement information along cables 151A, 154A).

[0360] In some embodiments, multiple measurement readings from a sensor 151 within a wall of a plasma delivery tip 66 are indirect indications of plasma temperature, provided that the measurements may also be affected by the heat absorption and / or heat conduction characteristics of the wall in the presence of plasma. Optionally, the multiple readings are calibrated, such as according to an equilibrium temperature and / or according to multiple rates of temperature change, to multiple corresponding plasma temperatures measured previously. In some embodiments, a sensor (such as sensor 154) includes a temperature sensor, such as a thermocouple, placed at a location that primarily indicates the external temperature of the plasma delivery tip and / or the plasma plume itself. Sensor 154 is shown as being exposed on an outer wall of plasma delivery tip 66. Optionally, an external sensor is brought into an operating position to detect the temperature of the plasma delivery tip and / or in its vicinity from another probe.

[0361] Optionally, any one of sensors 151, 152, 153, 154 includes a contact and / or proximity sensor. Optionally, the sensor includes an electrode, and sensing contact and / or proximity includes detecting multiple changes in impedance (such as resistance) experienced as the electrode moves with the plasma delivery tip 66 in its environment.

[0362] Now refer to Figure 2A , which schematically depicts a plasma delivery tip 66 configured with an adjustable length plasma discharge electrode 106 according to some embodiments of the present invention.

[0363] In some embodiments, the discharge electrode 106 includes a wire (such as a superelastic wire) that can be advanced (upper figure) relative to a shielded portion of an electrical conduit 105 and / or retracted (lower figure) into a shielded portion of the electrical conduit 105, wherein the size of the hollow 107A of the insulating sheath layer 102 is designed to accommodate more or less winding. In some embodiments, the dielectric barrier 103 is shape-changed (such as according to a change in the lumen diameter of any one of the embodiments shown and / or described regarding Figures 1B to 1G ), and the winding radius of the electrode 106 is increased or decreased to accommodate such changes.

[0364] Increasing the number of the multiple windings of the electrode 106 also changes the effective longitudinal length of the electrode 106. Optionally, this is used to adjust the multiple plasma generation characteristics of the plasma delivery tip 66, wherein a longer electrode may generate more and / or more concentrated plasma than a shorter electrode. The increase in plasma generation may be accompanied by a trade-off of increased heating, and thus a shorter electrode may be preferred in some cold plasma delivery scenarios.

[0365] Now refer to Figure 2B, which schematically illustrates a plasma delivery tip 66 configured with an adjustable diameter plasma discharge electrode 106B according to some embodiments of the present invention. Figure 2C , which schematically shows some embodiments of the present invention Figure 2B An end view of the adjustable diameter plasma discharge electrode 106B.

[0366] Electrode 106B is configured as a strip of conductive material shaped as a ring having a cutout 220. Cutout 220 may optionally be diagonal; for example, as shown (e.g., tilted relative to a radial direction) and / or tilted relative to a longitudinal axis extending through electrode 106B. Conductor 106A (e.g., a center conductor of electrical conduit 105) interconnects electrode 106B to a power source. When dielectric barrier 103 has a relatively large lumen diameter (above, for example, with respect to Figures 1B to 1G 106B), the electrode 106B assumes a corresponding extended configuration. When the dielectric barrier 103 has a relatively small lumen diameter (below), the electrode 106B assumes a more self-overlapping configuration. Optionally, the electrode 106B is partially self-overlapping even in its maximum expanded state. The gap in the electrode 106B and / or multiple overlaps in the electrode 106B may introduce some asymmetry in the shape of the generated plasma plume. The overlaps are optionally in the same plane as the ring, and / or overlap along a longitudinal axis.

[0367] Reference now Figure 2D , which schematically illustrates a plasma delivery tip 66 configured with an adjustable diameter plasma discharge electrode 106C according to some embodiments of the present invention.

[0368] When the dielectric barrier layer 103 is at a relatively small diameter, the electrode 106C is assumed to have a shape of a wave and / or zigzag pattern. As the layer 103 expands, the multiple waves / zigzags straighten, thereby allowing the diameter of the electrode 106C to expand as well. Optionally, the electrode 106C is formed of a superelastic material such as Nitinol. Optionally, the electrode 106C includes a conductive material printed, painted or otherwise deposited on an elastic support substrate.

[0369] Reference now Figure 2E , which schematically illustrates a plasma delivery tip 66 configured with a lasso-type adjustable diameter plasma discharge electrode 206D according to some embodiments of the present invention. Figure 2F , which schematically illustrates a plasma delivery tip 66 configured with an open-loop adjustable diameter plasma discharge electrode 206E according to some embodiments of the present invention.

[0370] In some embodiments, either of electrodes 206D, 206E can be tightened (reduce their diameters) by manipulating (e.g., pulling) a tension member 206A. Additionally or alternatively, electrode 206E can be tightened by manipulating the returned loop electrode portion 216. In some embodiments, the loop portion 216 goes all the way back to a control member. In some embodiments, the loop portion 216 is anchored in certain positions, such as to the side of the plasma delivery tip 66.

[0371] Optionally, the tension member 206A is also a conductor of the electrical conduit 105. Shrinking electrodes 206D, 206E also compresses the dielectric barrier layer 103, and correspondingly, in some embodiments, reduces the lumen diameter of layer 103. Optionally, relaxing the loops of electrodes 206D, 206E allows layer 103 (and its lumen diameter) to expand.

[0372] In some embodiments, electrode 206E extends around at least 75% of the circumference of the dielectric barrier layer 103. It should be noted that any radial asymmetry of a discharge electrode potentially causes a corresponding asymmetry in a plasma plume generated by a plasma delivery tip.

[0373] The insulating layer 202 is optionally implemented as an annular washer surrounding electrodes 206D, 206E. Optionally, the insulating layer 202 is embodied in other ways (e.g., as a tube in which electrodes 206D, 206E are at least partially embedded); for example, according to any of the Figures 1B to 1G multiple configurations shown and / or discussed.

[0374] Now refer to Figure 2G , which schematically shows a plasma delivery tip 66 configured with a helical adjustable length plasma discharge electrode 206F according to some embodiments of the present invention.

[0375] Optionally, the helix of the plasma discharge electrode 206F expands and contracts longitudinally passively due to the longitudinal expansion / contraction of layer 202A and / or layer 103, such as when implemented by one of the Figures 1B to 1G multiple configurations. Optionally, directly control the longitudinal dimension of electrode 206F, such as by pulling a member 206A to expand, and the member 206A can be a central conductor of the electrical conduit 105. In some embodiments, the expansion is controlled by heating (e.g., by heating a superelastic alloy whose shape expands when exceeding its transition temperature). In some embodiments, the expansion is controlled by using a magnetic field, optionally a magnetic field induced outside the plasma delivery tip.

[0376] Now refer to Figures 2H to 2J, which schematically shows a plasma delivery tip 66 configured with a segmented expansion distal end according to some embodiments of the present invention.

[0377] In some embodiments, a distal end of a plasma delivery tip 66 is configured with a circumferential arrangement of a plurality of layered portions 207, 208, 221, the plurality of layered portions being configured to mutually transform between a folded configuration (above) and an expanded configuration (above), wherein the plurality of layered portions 207, 208, 221 radially expand outward. The plurality of layered portions are optionally self-expanding (e.g., they are elastically inclined to expand when exiting a confinement sheath, not shown), expand by loosening their electrodes (e.g., as described with respect to Figures 2E to 2F and / or 3B), and / or can be expanded by another method.

[0378] In some embodiments, the plurality of layered portions include a plurality of portions of a folding element 208A ( Figure 2I , above), which expand into a circumferentially complete shape (below). Figure 2H A plurality of layered portions 207 are shown, which initially overlap and expand into an adjacent configuration of "barrel side plates", the expansion being optionally limited by the expanded diameter of the discharge electrode 206L. Optionally, the expanded configuration of the plurality of layered portions 207 maintains a small amount of overlap, which helps to maintain a complete circumference. In some embodiments, ( Figure 2J ), the plurality of layered portions 221 expand to leave a plurality of gaps between them. Although this may allow plasma supply gas to escape through the plurality of sides, the plurality of gaps may be small enough such that, under multiple laminar flow conditions, the plasma escaping from the sides can be negligible. Optionally, gas escape is prevented by a webbing between the plurality of layered portions 221 and / or an expansion liner of the lumen of the plasma delivery tip 66.

[0379] The discharge electrodes 206L, 206G ( Figure 2H - 2I ) are optionally circular in shape themselves when expanded, the circle being folded as needed to accommodate the folded configuration of the plurality of layered portions 207, 208. In the folded configuration, although the expanded configuration (the configuration that can generally provide the most and / or most concentrated plasma without overheating) may provide a more uniform and / or predictable plasma plume, the electrodes 207, 208 may still be operable. The plurality of dielectric properties of the plurality of layered portions 207, 208 help to determine the plurality of discharge characteristics that affect plasma generation within the lumen. The outer insulation of the discharge electrodes 207, 208 is optionally provided by a plurality of expansion rings 202 or an expansion tube. Optionally, the discharge electrodes 207, 208 are embedded in the material of the plurality of layered portions 207, 208 so as to be electrically insulated from all sides.

[0380] Optionally, the discharge electrode 206H includes a plurality of protrusions 223 extending into the plurality of layered portions 221 ( Figure 2J , only one protrusion is shown). Optionally, the plurality of protrusions 223 include a plurality of terminal extensions, and most plasma generation occurs conversely. External electrical insulation is optionally provided as a plurality of separate extensions 222, a ring, a tube, or by embedding the plurality of protrusions 223 within the material of the plurality of layered portions 221. Optionally, Figure 2J the embodiment of

[0381] Steering and tip shape options

[0382] Now refer to Figure 3A , which schematically shows a plasma delivery tip 66 configured with a manipulable end according to some embodiments of the present invention.

[0383] In some embodiments, the electrical conduit 105 and / or a conductor and / or a cable portion of the electrical conduit 105 may be slidable relative to the internal dielectric barrier layer 103, but connected to a distal end of the layer 103 such that, for example, tension applied to the electrical conduit 105 or a portion of the electrical conduit 105 causes the layer 103 to bend. Optionally, the discharge electrode 206J includes, for example, a circular wire, or has another electrode design, such as one of those described herein; for example, a mesh, a helix, and / or a split band. The electrode 206J is optionally insulated by an outer insulating layer 202.

[0384] Now refer to Figure 3B , which schematically shows a plasma delivery tip 66 configured with an end according to some embodiments of the present invention, the end being configured to contract into a penetrating cone.

[0385] In some embodiments, the electrode 206K is configured with a lasso or other constricting electrode design that can be tightened sufficiently to narrow a distal end 204 of the dielectric barrier layer 203A to a pointed tip that can be used, for example, for penetration resistance and / or to assist in guiding forward navigation. Optionally, the point reduces the far-side aperture of the layer 203A to less than its unconstricted diameter; for example, less than 50% or 25% of its unconstricted diameter. Optionally, the distal end 204 is beveled circumferentially (taper beveled) to reduce the amount of material that gathers together when the electrode 206K is tightened. Additionally or alternatively, the material near the tip is stretched to help sharpen the tip.

[0386] Now refer to Figure 4, which schematically shows a plasma delivery tip 66 configured with a beveled distal end according to some embodiments of the present invention.

[0387] In some embodiments, the beveled slice hypotenuse 408 optionally helps the plasma delivery tip 66 penetrate resistance and / or helps guide forward navigation. Within the plasma delivery tip 66, any of the electrode and insulation designs already described for a blunt-end plasma delivery tip 66 may be optionally provided; for example, the electrical conduit 105, the discharge electrode 106, the space 107, the sheath layer 102, and / or the dielectric barrier layer 103.

[0388] Optionally, a plurality of tubular portions near the plasma delivery tip 66 are provided with a mesh reinforcement 411 and / or a coil reinforcement 412 that act as a plurality of stiffeners. This potentially allows the plasma delivery tube including the plasma delivery tip 66 to act as its own guide when navigating to an internal body location where plasma is to be delivered. Such stiffeners are optionally provided to assist in the navigation of any of the plurality of plasma delivery tips described herein. It should be particularly understood that Figure 3A the steering configuration is also optionally provided to a plurality of embodiments having Figure 4 the plurality of features.

[0389] Now refer to Figure 5A , which schematically shows a plasma delivery tip 66 configured with a channel insulation tube 502 according to some embodiments of the present invention. Also refer to Figure 5B , which schematically shows a plasma delivery tip 66 configured with a helical channel insulation tube 502B according to some embodiments of the present invention. Further refer to Figure 5C , which schematically shows, according to some embodiments of the present invention, Figures 5A to 5B an end view of a cross-section of the channel insulation tubes 502, 502B. Also refer to Figure 5D , which schematically shows a plasma delivery tip 66 configured with a helical channel insulation tube 502C according to some embodiments of the present invention.

[0390] In Figures 5A to 5D all of the plurality of examples of Figure 5A a straight (layer 502, Figure 5B ) or helical (layers 502B, 502C, 5D ) channels 510, 511, 512. Figure 5BShows a cross-section of a channel that generates such, including a plurality of circumferentially arranged protrusions 521, separated by a plurality of notches 522. The plurality of channels are optionally surrounded by a protective sleeve 101. Optionally, the plurality of channels are formed as a plurality of tubes longitudinally passing through an insulating layer. Also shown are the circumferential positions of the dielectric barrier layer 103 and the discharge electrode 106.

[0391] When the plasma plume 10 introduces gas, for example, into a confined body space, the gas volume and / or pressure may increase. The channels 511, 512, 513 are optionally configured to relieve such accumulation, and the gas accumulation relief can be passive (i.e., a proximal end of a tube communicating with the channels 511, 512, 513 is open to the ambient pressure), and / or active (e.g., a suction pump is optionally applied to a proximal end of a tube communicating with the channels 511, 512, 513).

[0392] The gas interacting with the environment may thereby be cooled, so that when it returns, it can absorb some heat from the plasma delivery tip 66. Returning through a helical channel has a potential advantage of increasing this reverse cooling effect, for example, by increasing the path length that can absorb heat. Optionally, a coolant fluid (e.g., a gas or a liquid) is delivered through one or more of the channels 511, 512, 513. Optionally, the coolant fluid returns through another or more of the channels 511, 512, 513.

[0393] A potential problem when the ionized gas is transported back along the outer sides of the insulating layers 502, 502B, 502C is that it itself may be affected by multiple electric fields at or near its breakdown voltage, resulting in the induction of ectopic plasma. In some embodiments, the insulating layer itself is made of a dielectric material thick enough to ensure prevention of this situation. In some embodiments, an auxiliary gas is mixed with the ionized gas in the region where the plasma is generated to increase the breakdown voltage of the gas before the gas is depleted.

[0394] Multiple gas-surrounded discharge electrode configurations

[0395] Now refer to Figure 6A , which schematically shows a plasma delivery tip 66 including a discharge electrode assembly 601 according to some embodiments of the present invention, the discharge electrode assembly 601 being positioned within the lumen of a gas supply tube 603. Also refer to Figure 6B , which schematically shows the multiple position adjustments of the discharge electrode 606 within a plasma delivery tip 66 according to some embodiments of the present invention.

[0396] In some embodiments, the discharge electrode assembly 601 includes a discharge electrode 606 encapsulated within a dielectric resistance layer 602 and sized to be located within a lumen 610 of a gas supply tube 603. The discharge electrode assembly 601 is coupled to a voltage source via a coaxial cable 605 (and / or another electrical conduit), allowing for the establishment of a plasma generation voltage field within an air flow 8 through the lumen of the gas supply tube 603. Ionization within the air flow 8 generates plasma, which exits the lumen 610 as a plasma plume 10.

[0397] One potential advantage of this design is that it is particularly suitable for multiple small-diameter probes, as it allows for the production of multiple devices with fewer required functional layers. Optionally, the design allows for the conversion of a lumen (e.g., a working channel) of an existing multiple device into a gas supply tube by inserting the discharge electrode assembly 601, its cables, and any optional multiple positioning supports (e.g., as described with respect to Figures 6C to 6G ); and by attaching to an ionized gas source.

[0398] Optionally, control of multiple plasma parameters such as plasma temperature is performed by controlling the ionized gas flow rate, pulsed ionized gas flow, and / or dynamically mixing the ionized gas flow with other multiple gases to control ionization sensitivity and / or atomic mass.

[0399] In some embodiments ( Figure 6B ), the discharge electrode assembly 601 may be movable within the gas supply tube 603. The movement may optionally be along a longitudinal axis (e.g., Figure 6B upper and lower figures), and / or radially ( Figure 6B right figure). These movements are optionally performed to adjust plasma generation, multiple plasma plume characteristics, and / or multiple heat transfer characteristics. For example, multiple movements of the discharge electrode assembly 601 to multiple different depths within the gas supply tube 603 potentially allow for the positioning of a location where plasma generation efficiency, temperature, and plasma plume length are optimal for a current target and / or target position. Multiple movements of the discharge electrode assembly 601 to multiple different depths also potentially allow for the adjustment of the distance to a target surface.

[0400] Extruding the discharge electrode assembly 601 from the gas supply tube 603 may place it in a region of reduced plasma supply gas concentration, but may allow for greater selectivity of the internal body locations targeted for plasma delivery.

[0401] Moving the discharge electrode assembly 601 to multiple more radially offset positions within the lumen 610 of the gas supply tube 603 may affect the intensity, shape, and / or position of the generated plasma plume 610.

[0402] Now refer to Figures 6C to 6D, which schematically shows a positioning support 621 configured to be used with a plasma delivery tip 66 according to some embodiments of the present invention, the plasma delivery tip 66 including a discharge electrode assembly 601 positioned within a lumen of a gas supply tube 603. Figure 6C shows a blunt-ended gas supply tube 603, while Figure 6D shows a pointed-end (beveled) gas supply tube 603B, optionally serving as a needle or trocar tip for penetrating tissue.

[0403] In some embodiments, the positioning support 621 includes an exhaust disk on which the discharge electrode assembly 601 is mounted. For example, an electrical conduit 605 that supports the discharge electrode assembly 601 itself passes through a center of the positioning support 621, thereby helping to maintain a centered position of the discharge electrode assembly 601 while allowing the discharge electrode assembly 601 to move longitudinally along the lumen 610.

[0404] The positioning support 621 is vented to allow supply gas to pass through and / or over it. During plasma delivery, the flow of the gas is in a distal direction. Optionally, the direction of the gas flow is reversed to remove gas from a working area (e.g., by suction). During the reverse flow, plasma generation is optionally paused. In some embodiments, during a plasma delivery process in an area, the delivery of plasma and the removal of gas are alternated several times. The exhaust of the positioning support 621 includes, for example, a plurality of notches and / or a plurality of perforations around the circumference of the positioning support 621.

[0405] Figure 6C a plurality of optional ventilation holes 622 (implemented as a plurality of holes) of and / or Figure 6E a plurality of optional ventilation holes 623 (implemented as a plurality of slots) of can be provided as an additional or alternative feature to allow the exhaust of the ionized gas. This is a potential advantage to allow the plasma delivery tip to be pressed against a target surface to be treated without causing multiple pressure instabilities and / or multiple contact interruptions due to the accumulation and uncontrolled release of the ionized gas during plasma generation. Optionally, exhausts (e.g., using shapes similar to the ventilation holes 622, 623 or other shapes) are provided to any of the plasma delivery tip embodiments described herein (e.g., Figures 1B to 1G and / or any of 2A to 2J).

[0406] Now refer to Figures 6E to 6G , which schematically shows a positioning support that allows longitudinal and radial position adjustment of a plasma delivery tip 66 according to some embodiments of the present invention, the plasma delivery tip 66 including a discharge electrode assembly 601 positioned within a lumen of a gas supply tube 603.

[0407] In some embodiments, the positioning support for the discharge electrode assembly 601 includes a rotary positioning support 631 and a slotted positioning support 632. The discharge electrode assembly 601 is mounted to a member (such as coaxial cable 605) that extends longitudinally within the lumen 610 of the gas supply tube 603. The coaxial cable 605 passes through the rotary positioning support 631 at a position 641 (such as a hole) that is radially offset from the center of the lumen 610. It also passes through the slotted positioning support 632 at a slot 642 that radially traverses the lumen 610.

[0408] When the coaxial cable 605 rotates, the rotary positioning support 631 also rotates. This causes the coaxial cable 605 (at the intersection) to move along a circular path. Distally, the slot 642 restricts the coaxial cable 605 so that it re-centers along one axis, but remains free to move back and forth along a substantially orthogonal axis. As a result, the discharge electrode assembly 601 is restricted to move along a narrow elliptical and / or substantially linear path when the coaxial cable 605 to which it is mounted rotates.

[0409] The amount of "wobble" (bending and / or translational movement along the restricted axis) in the movement of the discharge electrode assembly 601 caused by the offset of the position 641 from the slot 642 is optionally set by adjusting the relative distances of the discharge electrode assembly 601 and the rotary positioning support 631 and the slotted positioning support 632. Optionally, the thickness of the slotted positioning support 632 along a proximal-to-distal axis of the lumen 610 is made greater to reduce and / or prevent wobbling.

[0410] Optionally, the slotted positioning support 632 is rotatably and / or fixed along a proximal-to-distal axis of the lumen 610 within the lumen 610; for example, by interference and / or friction with the shape of the multiple walls of the gas supply tube 603.

[0411] Now refer to Figures 7A to 7D , which schematically shows a plurality of adjustable discharge electrodes 706A, 706B, 706C, 706D of various discharge electrode assemblies configured to be positioned within a lumen of a gas supply tube according to some embodiments of the present invention.

[0412] The adjustable discharge electrode 706A ( Figure 7A ) includes a plurality of pointed teeth 711 that can be actuated to expand or contract within a capsule space 712 formed within the dielectric barrier layer 702. Actuation includes, for example, a plurality of longitudinal movements of a cable 715 (which can also be a central conductor of a coaxial cable 705) to move the plurality of pointed teeth into and out of a restricting outer sleeve 713 (which can include, for example, one or more surrounding layers of a coaxial cable 705). Optionally, the plurality of pointed teeth 711 are formed of a superelastic material, such as nitinol.

[0413] Additionally or alternatively, in some embodiments, the plurality of teeth 711 are self-actuating as a function of temperature. For example, the plurality of teeth 711 optionally include a shape memory alloy (e.g., nitinol), having a transition temperature set to change the shape of the discharge electrode 706A to a less efficient plasma generation configuration when hot. This provides a potential advantage for reducing or preventing overheated plasma delivery to tissue. The plurality of shape memory effects are optionally used to provide thermal self-actuation of other electrode shapes, such as any of electrodes 706B, 706C, 706D.

[0414] In some embodiments, a plurality of thermally actuated shape changes (e.g., a plurality of thermally actuated shape changes of a discharge electrode or other discharge circuit element) are used to provide temperature monitoring; e.g., by measuring a plurality of changes in a plurality of circuit characteristics caused by the plurality of shape changes.

[0415] The adjustable discharge electrode 706B ( Figure 7B ) includes a helix (e.g., a helical spring). Optionally, a length of the discharge electrode 706B is adjusted within the capsule space 712 by a plurality of longitudinal movements along a proximal-to-distal axis of a control member 716 attached to the discharge electrode 706B.

[0416] The adjustable discharge electrodes 706C, 706D ( Figures 7C to 7D ) each include a collapsible mesh. Optionally, a length of the discharge electrode 706C is adjusted within the capsule space 712 by a plurality of longitudinal movements along a proximal-to-distal axis of a control member 716 attached to the discharge electrodes 706C, 706D. In Figure 7D the described embodiment, the adjustment also moves the dielectric discharge barrier 702 relative to the coaxial cable 705. Optionally, this allows the discharge electrode 706D to effectively fill any size capsule space 712.

[0417] Now referring to Figure 8A , which schematically shows a discharge electrode assembly 801 configured to be positioned within a lumen of a plasma supply tube and including a dielectric barrier layer 802 adjustable by inflation. The discharge electrode assembly 801 represents a plurality of specific embodiments of a discharge electrode assembly 601 and is optionally provided with any suitable plasma supply tube, discharge electrode, and / or positioning support, such as described herein with respect to Figures 6A to 7D .

[0418] In some embodiments, the dielectric barrier layer 802 can expand from a folded configuration (upper figure) to an extended configuration (lower figure); for example, by injecting a fluid (gas or liquid) through the gas injection tube 803 to expand the expandable lumen 804. Optionally, inflation is performed by applying axial compression to the dielectric barrier. The expansion changes the plurality of dielectric barrier properties of the dielectric barrier layer 802, thereby changing the plurality of plasma generation and / or plasma plume properties (e.g., a thicker barrier reduces plasma generation and / or increases the plasma breakdown voltage). In some embodiments, inflation is initiated by heating a volatile liquid within the lumen 804 (optionally, without using a gas injection tube 803), thereby providing a feedback mechanism that reduces power dissipation in response to a plurality of elevated temperatures. This has a potential advantage for device safety. Optionally, another temperature-sensitive transition is provided for adjusting the plurality of material properties of the dielectric barrier layer 802, e.g., a solid that melts into a fluid, or a gas that expands. Optionally, a shape memory alloy or polymer having a temperature-dependent expansion or contraction shape is placed within the lumen 804 to change its shape.

[0419] Now referring to Figure 8B , which schematically shows a discharge electrode assembly 810 configured to be positioned within a lumen of a plasma supply tube and including a multi-thin-layer dielectric barrier layer 812, in accordance with some embodiments of the present invention.

[0420] The adjustable discharge electrode assembly 810 represents a plurality of specific embodiments of a discharge electrode assembly 601, and is optionally provided with any suitable plasma supply tube, discharge electrode, and / or positioning support, such as described herein with respect to Figures 6A to 7D .

[0421] In some embodiments, the dielectric barrier layer 812 includes a plurality of layers 812A, 812B, 812C that are configured to slide past one another to longitudinally expand or contract the discharge electrode assembly 810. In the extended configuration (upper figure), the discharge electrode 606 is surrounded by a relatively thin dielectric barrier, which includes, for example, only the thin layer 812C. In the folded configuration (lower figure), the discharge electrode 606 is surrounded by a relatively thick dielectric barrier layer, which includes, for example, the thin layers 812A, 812B, and 812C. Changing the total dielectric barrier thickness changes the plurality of dielectric barrier properties of the dielectric barrier layer 812, thereby potentially changing the plurality of plasma generation and / or plasma plume properties (e.g., a thicker barrier reduces plasma generation).

[0422] Actuation is optionally performed, e.g., by applying pressure to longitudinally advance the electrical conduit 105 and / or a portion of the electrical conduit 105 (e.g., a conductor connected to the electrode 606), while keeping the thin layer 812A restricted (e.g., anchored to a wall of a gas delivery tube and / or anchored to an outer layer of the electrical conduit 105). Optionally, the electrical conduit 105 and / or the thin layers 812A, 812B, 812C are provided with a plurality of mechanical stops to prevent over-drawing and / or over-extension.

[0423] Now refer to Figure 9 , which schematically shows a discharge electrode assembly 601 and an electrical conduit 905 (an example of an electrical conduit 105) according to some embodiments of the present invention, which is configured to act as a guide wire for guiding the advancement of the gas supply tube 603. In addition to its function as a shield transmitter of electrical power, the electrical conduit 905 is optionally constructed mechanically to act as a guide wire for the gas supply tube 603; the two together constitute multiple elements of a catheter system. Optionally, a standard catheter guide wire having another hollow core is provided with a wire 903 extending along the hollow core (with additional electrical insulation if needed) to form a combined guide wire / electrical power transmission line. Optionally, the wire 903 is also a control wire, which is operable, e.g., to actuate steering at a distal tip of the electrical conduit 905.

[0424] Optionally, a discharge electrode and / or a dielectric barrier layer of the discharge electrode assembly 901 is configured as any of the plurality of discharge electrode assemblies described herein; e.g., in Figures 6A to 7D . Optionally or additionally, a tip of the discharge electrode assembly 901 is tapered and / or pointed, which may assist in forward navigation. Optionally, the tip of the electrode is rounded to provide a non-damaging tip for advancement within a plurality of body cavities.

[0425] Optionally, any part of the discharge electrode assembly 901 is provided with a radiopaque marker material. Optionally, an electrode 906 of a discharge electrode assembly 901 includes a conductive material (e.g., gold, silver, and / or platinum), which is also a radiopaque material.

[0426] Now refer to Figures 10A to 10C, which schematically shows alternative tools 1001, 1102, 1003 optionally using a gas supply tube 603 according to some embodiments of the present invention. In some embodiments, the medical tool used includes a longitudinally extending member that is long enough to extend from a proximal side of the gas supply tube 603 to a distal side of the gas supply tube and thin enough to be inserted into the gas supply tube 603. In some embodiments, the medical tool terminates in a device for cutting, dissecting, penetrating, cauterizing, sampling, or otherwise treating tissue located near the distal side of the gas supply tube. In some embodiments, the medical tool terminates in a non-invasive tip (such as a non-invasive tip of a guide wire), optionally tapered to assist in advancing the tool into an aperture of a body cavity.

[0427] In some embodiments, a gas supply tube 603 is configured to supply an ionized gas that is converted into a plasma by a discharge electrode assembly 601, and the gas supply tube 603 can optionally be converted in situ into a working channel by removing its discharge electrode assembly 601 and inserting another medical tool. Multiple examples of such medical tools include a guide wire 1001, a cutter 1002, and a cautery electrode 1003.

[0428] In some embodiments, a discharge electrode 106 circumferentially extends around a gas delivery lumen of the gas supply tube 603 (e.g., as described regarding Figures 1B to 4 ), and the lumen of the gas supply tube 603 can be used as a working channel by inserting a tool such as a guide wire 1001, a cutter 10002, and / or a cautery electrode 1003.

[0429] Multiple potential advantages of this configuration include reducing the replacement of multiple tubes during a procedure using multiple tools, and / or allowing the gas supply tube 603 itself to be the largest diameter tube in a procedure (which is a potential advantage in reducing power density).

[0430] Multiple discharge electrodes separate from multiple gas delivery lumens

[0431] Now refer to Figures 11A to 11D , which schematically shows multiple different arrangements of multiple lumens for ionized gas delivery, plasma / ionized gas removal, and / or current delivery according to some embodiments of the present invention.

[0432] Figure 6A (For example) shows a configuration in which an ionized gas stream 8 is delivered through the same lumen 610 for delivering a discharge electrode assembly 601. For example, as Figures 11A to 11D shown, ionized gas delivery can optionally be through a lumen separate from the lumen for delivering the discharge electrode assembly 601.

[0433] In Figure 11AIn a plasma device tip 1101, a gas delivery lumen 1102 and a working channel 1103 are included, and the working channel 1103 is configured to allow access to its end through a discharge electrode assembly 601. A plasma plume 10 is generated outside the plasma device tip 1101, where an ionized gas flow 8 is close to the discharge electrode assembly 601. Optionally, the plasma device tip 1101 includes a distal extension (not shown), where the gas flow 8 is kept restricted, and the discharge electrode assembly 601 can also be advanced into it. Optionally, the lumen 1102 is alternately used to supply the ionized gas and remove gas from the working site. Optionally, the lumen 1103 itself is configured to transport and / or remove the ionized gas. Optionally, its lumen is larger than a diameter of the discharge electrode assembly 601, and / or the discharge electrode assembly 601 is fully extruded from the lumen 1103 during operation to allow gas to enter and exit the lumen 1103.

[0434] Optionally ( Figure 11C ), the plasma and / or ionized gas is removed by suction from another lumen 1107 introduced into the area of plasma delivery. Additionally or alternatively ( Figure 11B ), a plasma device tip 1110 includes a plasma / gas removal lumen 1105 in addition to the gas delivery lumen 11102 and the working channel 1103.

[0435] In some embodiments, all three lumens are provided on multiple separate probes; for example, the discharge electrode assembly 601 is transported through the lumen 1121, the ionized gas is transported through the lumen 1123, and the plasma / ionized gas is removed through the lumen 1107.

[0436] One potential advantage of generating plasma outside a confinement lumen is a reduction in hot spot accumulation. Optionally, the plasma flow can be guided more flexibly; in addition, moving the ionized gas flow may also result in a reduction in hot spot accumulation. Optionally, a plasma plume with a diameter larger than the inner diameter of the lumen supplying the ionized gas can be generated.

[0437] Another potential advantage is to allow plasma to be generated in multiple cavities that are too small to introduce an entire plasma delivery tip including a delivery lumen, but large enough to allow introduction of the electrode assembly and the gas flow.

[0438] Multiple small-diameter discharge electrode assemblies

[0439] Now refer to Figures 12A to 12B , which schematically shows multiple structural details of a small-diameter discharge electrode assembly 601 according to some embodiments of the present invention.

[0440] In some embodiments, an outer diameter of the discharge electrode assembly 601 (for example, suitable for use with Figures 6A to 6GThose related to embodiments of the discharge electrode around which the flow occurs (an outer diameter) are constructed to include a distal extension of an electrical conduit 105 of a coaxial cable such that its maximum diameter is minimized to approximately the diameter of the electrical conduit 105 itself. This provides a potential advantage for establishing a complete plasma delivery tip 66 with a small size.

[0441] In some embodiments, the electrical conduit 105 includes an outer insulator 1201, an electrical shielding layer 1208, an inner insulator 1206, and a core conductor 1207. To form the discharge electrode assembly 601, the outer insulator 1201 and the electrical shielding layer 1208 are peeled off from the inner insulator 1206. On a part 1223 of the peeled area, a rigid or semi-rigid tube 1209 replaces the electrical shielding layer 1028. The tube 1209 optionally includes a solid metal (such as stainless steel) tube, a coil structure, or another rigid or semi-rigid structure. An outer insulator 1203 extends (optionally) on the tube 1209 (for example, it can even optionally be the original outer insulator 1201, returned to its original position). The outer insulator 1203 is optional because the potential of the rigid tube 1209 is optionally set to the same ground potential as the body in which the discharge electrode assembly 601 is to be operated.

[0442] A small portion of the core conductor 1207 extends distally beyond the area 1223. This portion is encapsulated by a dielectric barrier layer 1205, and a voltage is applied across the dielectric barrier layer 1205 to convert the ionized gas into cold plasma. Optionally, the dielectric barrier layer 1205 is blunt, or conversely ( Figure 12B ), a pointed dielectric barrier layer 1221 is provided. The pointed version provides a potential advantage of using the discharge electrode assembly 601 as the tip of a guide wire, for example regarding Figure 9 as described. Optionally, Figure 12B the pointed version can be used to penetrate tissue to access a target area.

[0443] Multiple side discharge plasma delivery tips

[0444] Now refer to Figures 13A to 13F , which schematically shows multiple plasma delivery tips 66 configured to generate inclined and / or vertical angles of multiple plasma plumes relative to a longitudinal axis of the plasma delivery tip 66 according to some embodiments of the present invention.

[0445] In some embodiments, an ionized gas flow 8 is at least partially directed to a side of a plasma delivery tip 1300, 1310, 1320, 1330, 1340, 1350, thereby generating a laterally directed plasma plume 10.

[0446] Figure 13A ,13D , 13E shows multiple examples where the discharge electrode 1303 and the corresponding dielectric barrier layer 1301 are positioned around (e.g., circumferentially around) one or more holes 1302, and the ionized gas flows through the holes 1302 to be ionized and generate one or more plasma plumes 10. In Figure 13A , a coaxial cable interconnects the discharge electrode 1303 with a high-voltage power supply, and the gas delivery tube 1307 includes a single hole 1302 on one side, just before a closed blunt distal end of the gas delivery tube 1307. In Figure 13D , the gas delivery tube 1331 includes a closed sharp distal end (optionally hollow or solid) having a laterally facing hole. The sharp distal end is optionally used for navigation within a body cavity and / or tissue penetration. In Figure 13E , the gas delivery tube 1341 includes multiple holes 1302; as shown, two lateral holes and one distal hole. Optionally, the corresponding multiple discharge electrodes 1303 are interconnected by multiple link connections to receive the high-voltage power supply for electric power.

[0447] Figure 13F shows a lateral hole configuration where a discharge electrode assembly 601 is located within a gas delivery tube 1351, and the resulting plasma plume 10 is guided outward from a laterally facing hole. Optionally, a similar electrical design is provided for Figures 13D to 13E the holes and the sharpened or open end configurations.

[0448] Figure 13B and 13C show other aperture designs; an inclined guide hole 1312 of a gas delivery tube 1311 ( Figure 13B ) and a rearwardly inclined guide hole 1322 of a gas delivery tube 1321 ( Figure 13C ). Regarding Figure 13A and 13D of the two electrical configurations discussed up to 13F, either one is optionally provided to Figures 13B to 13C any one of the multiple embodiments; that is, gas around the electrode, or electrode around the gas.

[0449] Multiple off-axis discharge plasma delivery tips

[0450] Now refer to Figure 14A , which schematically shows the scanned delivery of cold plasma to a body cavity 50 according to some embodiments of the present invention.

[0451] In some embodiments, the direction of a plasma plume 10 can be changed by steering. Figure 14Ashows movement of a distal end of a plasma delivery tip 66 within a body cavity 50 between a first position 1405A and a second position 1405B (the dashed lines reflect the same device shown in two different positions separated by time and device movement). The movement is optionally actuated, for example, by a tip steering mechanism or another steering mechanism as described with respect to Figure 3A or another steering mechanism.

[0452] Now referring to Figure 14B , which schematically shows a plasma delivery tip 66 configured for angular scanning from within a sheath tube 101 according to some embodiments of the present invention.

[0453] In some embodiments, a plasma delivery tip 66 can be maneuvered from within a sheath tube 101, allowing it to bend inward to change an angle of a plasma plume 10, optionally without corresponding movement of the sheath tube 101. This is a potential advantage, for example, for guiding plasma from a restricted space and / or a hard passage that limits movement of the sheath tube 101 (such as a passage through bone) to multiple different locations.

[0454] Optionally (e.g., as shown by the difference between the left and right figures of Figure 14B ), actuation includes changing the tension on a member attached near the distal end of the plasma delivery tip 66; for example, a portion of an electrical conduit 105. Figure 14B The example of Figures 1A to 2H also shows an insulating sheath layer 102 defining an electrode receiving space 107, a dielectric barrier layer 103, and a discharge electrode 106; alternatively, other configurations of these and / or other features can be provided optionally (e.g., as described with respect to

[0455] Now referring to Figure 14C , which schematically shows a plasma delivery tip 66 configured for wire-guided scanning by bending a gas delivery tube 603 according to some embodiments of the present invention. Optionally, the bending occurs within a short distal region of the plasma delivery tip, such as the outermost 15 mm, 10 mm, or 5 mm of the plasma delivery tip. Bending a small portion of the plasma delivery tip has the potential advantage of scanning a plasma plume over a target without much additional maneuvering space.

[0456] In some embodiments, the angle of a distal hole of a gas supply tube 603 can be adjusted by a plurality of movements actuated near an exit hole of the gas delivery tube 603. In some embodiments, a control line 1401 extends slidably along the gas delivery tube 603 from a proximal side through an anchoring position. The anchoring position optionally includes, for example, a hole of a first tube insert 1402 (such as an inserted ring). The control line 1401 is further fixed along the gas delivery tube 603 to another anchoring position, which can include, for example, a second tube insert 1403 (such as an inserted ring). The anchoring positions differ by a radial offset (left figure). Tightening the control line 1401 tends to bring the anchoring positions closer together, resulting in (right figure) a change in the alignment of the anchoring positions (such as the inserts changing their relative radial alignment). This in turn causes a deflection of the gas delivery tube 603 (right figure), thereby causing a deflection of the angle of the plasma plume 10.

[0457] Figure 14C Shows the steering of a plasma plume 10 for a plurality of embodiments including a discharge electrode assembly 601 located within a lumen of a gas supply tube 603. The same mechanism is optionally provided within the lumen of an embodiment where the discharge electrode (such as a discharge electrode 106) surrounds the gas flow; for example, replacing Figure 14B the external tension cable arrangement shown. Conversely, the steering of a plurality of embodiments including a discharge electrode assembly 601 located within a lumen of a gas supply tube 603 is optionally provided by a cable mechanism, such as with respect to Figure 14B as described.

[0458] Now refer to Figures 15A to 15C , which schematically shows a plasma delivery tip 66 configured for rotational actuation scanning of a plasma plume according to some embodiments of the present invention.

[0459] In some embodiments, the position of a plasma plume 10 generated by a plasma delivery tip 66 is scanned within a medical sheath 101 by a rotational actuation including rotation of a guide insert 1501. The plasma delivery tip 66 passes through a radially offset hole of the guide insert 1501 from a proximal direction, and the guide insert 1501 is in turn positioned within the sheath 101. Thus, rotation of the guide insert 1501 causes a circumferential movement of the plasma delivery tip 66 within the sheath 101. Optionally, the rotation is achieved by direct rotation of the guide insert 1501. Optionally, rotation of a catheter (such as a portion of a probe catheter 73) attached to the plasma delivery tip 66 causes rotation of the plasma delivery tip 66 itself, and the guide insert 1501 is attached to the plasma delivery tip 66 such that it also rotates. Figures 15A to 15C Shows that this circumferential movement occurs in two steps, each step being approximately 90°.

[0460] Optionally, a circular motion at a distal end of the plasma delivery tip 66 is converted into a more linear motion by using an additional slotted guide insert 1503 located distal to the guide insert 1501. The slotted guide insert 1503 "filters" one axis of the circular motion, thereby reducing its amplitude, while the motion along the other axis remains free. Optionally, due to the forced radial offset in the plasma delivery tip 66 between the position of the insert 1501 and the position of the insert 1503, an angle is created along the axis of the reduced circular motion. The amplitude of the "swing" of this angle is optionally adjusted by changing the relative position of the two inserts along a proximal-to-distal axis, for example as described with respect to Figures 6E to 6G that described. Optionally, by fitting the holes of the guide insert 1503 to the size of the plasma delivery tip 66 in two directions, an angling of the two axes is caused (e.g., multiple movements that produce a conical pattern of the plasma plume 10).

[0461] Adjusting a plasma delivery tip

[0462] Now refer to Figure 16 , which is a schematic flow chart of a method for adjusting a plasma delivery tip according to some embodiments of the present invention.

[0463] In some embodiments, at block 1610, a plurality of target plasma generation parameters are selected. In some embodiments, the selection is direct; for example, a clear selection to increase or decrease the thickness of an inter-resistive layer, increase or decrease the lumen diameter of a gas delivery lumen, and / or increase or decrease the longitudinal extent of a discharge electrode. In some embodiments, the selection is through a proxy parameter; for example, a selection to increase power and / or decrease temperature. Optionally, the selection includes a selection of a predefined scenario or a range of scenarios; for example, a narrow plume or wide plume delivery of plasma, or a scenario prepared for treating a specific target type and / or organ tissue type.

[0464] In some embodiments, at block 1612, the plasma delivery tip is adjusted according to the plurality of selected plasma delivery parameters. The adjustment may optionally be direct; for example, an operator manipulates a slider or other control to adjust a thickness, diameter, or other dimension. In some embodiments, the adjustment is performed by making a selection along a scale (e.g., a scale of power, temperature, or an arbitrary scale), and / or by making a selection from a plurality of options. In some embodiments, the plasma processing apparatus automatically manipulates a plurality of parameters based on the selection along the scale or the selected option. Optionally, a plurality of parameters other than the plasma delivery tip configuration itself are adjusted; for example, the voltage output of a power supply, a delivery rate of an ionized gas, and / or a mixture of ionized gas species. In some embodiments, the adjustment is implemented by using logic circuitry; for example, a selection is made through a controller interface, and a controller actuates a plurality of changes (and other plurality of optional changes) to the plasma delivery tip based on the selection. The plurality of details of the actuation may optionally be stored as a plurality of computerized (digital) instructions and / or data.

[0465] In some embodiments, at block 1614, the plasma is generated using the adjusted plasma delivery tip.

[0466] Plasma delivery tip cross-sectional shapes

[0467] Now refer Figures 17A to 17D , which shows a plasma delivery tip 1710 according to some embodiments of the present invention, which expands its distal hole 1721 to a cross-section wider than the diameter of the sheath tube 1720 of the expansion tip 1700. Also refer Figures 18A to 18D , which shows other examples of wide cross-section distal holes 1820, 1830 according to some embodiments of the present invention.

[0468] Figures 17A to 17B In a transverse view ( Figure 17A ) and an end longitudinal view ( Figure 17B ) the same configuration of the tip 1710 is shown. In this configuration, the plasma delivery tip 1710 is constrained by the (circular) lumen wall of the sheath tube 1720.

[0469] Figures 17C to 17D In a transverse view ( Figure 17C ) and an end longitudinal view ( Figure 17D) shows another identical configuration of the tip 1710. In this configuration, the plasma delivery tip 1710 extends from the sheath tube 1720, allowing it to assume a rectangular (e.g., elliptical) configuration. This shape change can be driven by stored elastic energy when the material of the lumen wall 1701 of the tip 1710 (e.g., silicone rubber or another flexible polymer) is compressed to fit within the lumen of the sheath tube 1720. In some embodiments, a support ring 1722 is provided to assist in the expansion and / or stability of the extended tip. The support ring 1722 can, for example, be made of a superelastic metal such as Nitinol. Optionally, the support ring 1722 also serves as the discharge electrode of the plasma delivery tip 1710. Here and in Figures 18A to 18D In the for clarity of the present invention, the multiple indications of the electrical conduit 105 and / or alternative discharge electrode 106 embodiments are suppressed. Figures 1B to 3B Several principles are described, and these elements are optionally provided.

[0470] A potential advantage of the extended tip is to widen the plasma plume generated therefrom so that it is spread over a larger linear range than the inner diameter of the sheath tube 1720 delivering the tip 1710. This may be a combined effect of a change in the distribution of the ionized gas and a change in the shape of the electrode (e.g., attached to the lumen wall of the tip 1710), which ionizes the ionized gas.

[0471] Moving the widened plasma plume along an axis substantially transverse to the direction of widening in strokes can allow tissue surface areas to be "portrayed" with plasma in relatively fewer strokes, with more overlap, and / or with greater certainty that no gaps are left between adjacent strokes. Another potential advantage is that the average closest approach distance between ionized gas molecules and the discharge electrode itself may be reduced (e.g., the molecules in the center are not as far from the electrode as they are in a circular lumen). This, in turn, potentially helps to increase the efficiency of ionization effects exerted by the electrode on the ionized gas, and / or the efficiency of a cooling effect by which the ionized gas carries away heat generated by power losses near the electrode.

[0472] Figures 18A to 18D Shows optional Figures 17A to 17D Other examples of cross-sectional shapes that can be provided by the same principles described. Figures 18A to 18B A cross section of a crescent-shaped plasma tip is shown, which is confined by a sheath tube 1801 (resulting in Figure 18A A folded cross-section 1821), and after releasing the restriction ( Figure 18B The expanded cross-section 1820; compared with the inner diameter of the sheath tube 1801).Figures 18D to 18D shows a cross-section of a zigzag plasma tip confined by a sheath tube 1801 (resulting in Figure 18C a folded cross-section 1831), and after release of the confinement ( Figure 18D an expanded cross-section 1830; compared to the inner diameter of the sheath tube 1801).

[0473] Now refer to Figures 19A to 19F , which shows examples of multiple wide cross-sectional distal holes of plasma delivery tip tubes 1910, 1920, 1930 that themselves house discharge electrode assemblies 1912, 1922, 1932 having multiple elongated cross-sections according to some embodiments of the present invention. In some embodiments, electrode assemblies 1912, 1922, 1932 include an inner conductor (e.g., an example of a dielectric barrier layer 103) connected to an electrical conduit 1924 and embedded in an outer insulator, such as described for Figures 20A to 22C the discharge electrode assemblies 2020, 2120, 2220. Optionally, the dielectric barrier layer is omitted. For both types of discharge electrode assemblies, it is expected that the multiple plasma generation parameters will be different, and in the absence of the dielectric barrier layer, more current is expected to be delivered to the body of a patient compared to when using a dielectric barrier layer.

[0474] In some embodiments, any one of the discharge electrode assemblies 1912, 1922, 1932 can be moved separately from the respective plasma tip tube lumen that houses it. For example, the discharge electrode assemblies can optionally be actuated to advance from their respective sheaths by movement of their respective connected electrical conduits 1924; such as described for Figures 11A to 11D .

[0475] The electrode assemblies can be flexible to fold together with their enclosed tip lumens (e.g., in the case of plasma delivery tips 1903, 1905 and their discharge electrode assemblies 1922, 1932), or the width can be small enough that they do not need to fold to be held within a confinement sheath (e.g., in the case of plasma delivery tip 1901 and its discharge electrode assembly 1912).

[0476] Figures 19A to 19FIn the described embodiments, the shape of the discharge electrode is partially separated from the shape of the lumen through which the ionized gas flows because the electrode is not embedded in the wall itself. It should be noted in particular that plasma can still be generated when the discharge electrode assembly extends from its lumen, so that the shape of a plasma plume generated is partly determined by the shape of the electrode and partly depends on the way in which the lumen of the plasma delivery tip shapes the ionized gas flow. This separation potentially allows shaping the region of plasma generation and / or delivery to suit a variety of specific needs, such as the shapes of multiple specific tissue surfaces. In addition, the ionized species generated in the plasma may change along the length of a plasma plume when undergoing post-ionization equilibrium. For example, along a plasma plume of just a few millimeters, quenching of the primary ionized species, generation of secondary ionized species, may occur as the multiple primarily generated ions interact with each other and / or with the initial non-ionized species, and / or there is a redistribution of thermal energy. Depending on the circumstances, any of these can potentially affect multiple treatment effects. Advancing the discharge electrode from the gas delivery tube may allow control of the "freshness" of the plasma when it reaches the tissue because the discharge electrode itself is the site of initial plasma generation.

[0477] Multiple discharge electrodes

[0478] Now refer to Figures 20A to 20C , which schematically shows a width-expanded discharge electrode assembly 2020 for use with a plasma delivery tip 2001 according to some embodiments of the present invention. Also refer to Figures 21A to 21B , which schematically shows a different width-expanded discharge electrode assembly 2120 for use with a plasma delivery tip 2101 according to some embodiments of the present invention.

[0479] The width-expanded discharge electrode 2020 includes a flexible conductive sheet 2022 (optionally including a superelastic alloy such as nitinol), optionally insulated by a dielectric barrier layer 2021. When confined within the lumen of a tube 2010, the width-expanded discharge electrode assembly 2020 folds up and / or rolls up, as shown, for example, in Figure 20A .

[0480] Upon leaving the confinement of the tube 2010, the discharge electrode assembly 2020 flattens out. Figures 20B to 20C Shows the use of the flattened discharge electrode assembly 2020 to generate multiple plasma plumes.

[0481] In Figure 20BIn [the example shown], the discharge electrode assembly 2020 can be very close to a surface of the tissue wall 50 (in the example shown, including a surface of a treatment target 51), while an ionized gas flow 2035 (2035 refers to any one of the arrows indicating flow) emitted from the tube 2010 passes through it. The ionized gas flow 2035 can be slightly dispersed by deflection from the tissue wall 50 and / or as a function of the distance from the orifice of the tube 2010 from which it is emitted. Since all of the conductive sheet 2022 is at approximately the same potential and as long as its surface is well covered by the flowing ionized gas, the linear extent (in cross-section) of the plasma plume 2030 may be increased compared to the more "pencil-shaped" flow that might issue directly from the distal orifice of the tube 2010. Additionally, at least a portion of the plasma can be generated very close to the tissue wall 50, optionally all the way up to and including at multiple locations in substantial contact with the treatment target 51.

[0482] In Figure 20C [the example shown], the flat surface of the discharge electrode assembly 2020 is oriented generally parallel to the surface of the tissue wall 50. This has the potential to create a plasma plume 2031 that has a relatively large surface area in contact with the tissue wall 50, and in particular the area of the treatment target 51. This is a potential advantage for selectively delivering plasma while ensuring that the entire surface area of a treatment target 51 has been sufficiently saturated with treatment plasma. It can be noted that the discharge electrode assembly 2020 and the tissue wall 50 act together to partially confine the gas flowing between them, which may help increase the concentration of the plasma.

[0483] The distribution of the ionized gas is optionally assisted by one or more baffles located on any suitable surface of the discharge electrode assembly 2020, such as baffle 2041 (baffle 2041 is not shown in Figure 20B [the example shown], but optionally they are provided there as well). Multiple baffles in the form of multiple protrusions (such as multiple fins) from the assembly are formed to help distribute an ionized gas flow to form a wider plume over a greater extent of the electrode surface and / or to disperse the ionized gas, and are optionally provided as a component of any of the multiple discharge electrode assemblies described herein. In particular, multiple baffles can be used with multiple discharge electrode assemblies that expand and / or reorient as they are advanced from a confinement tube. The multiple baffles can help direct an ionized gas flow over a greater portion of the available surface area of the electrode.

[0484] In some embodiments, the discharge electrode assembly 2020 tapers proximally, so interference with the multiple walls of the tube 2010 forces it to roll up and / or refold as it is retracted back into confinement.

[0485] The conductor 2024 is used to deliver the discharge voltage to the discharge electrode assembly 2020 and is part of an electrical conduit 2023 (which is in turn an embodiment of an electrical conduit 105). The electrical conduit 2023 is optionally a coaxial cable or an insulated single-conductor cable.

[0486] It should be noted that there is no restriction on orienting the longitudinal axis of the lumen along which the multiple "plate" surfaces of the discharge electrode assembly 2020 are advanced. For example, the discharge electrode assembly 2020 can be preconfigured to be bent towards the vertical direction (e.g., at an angle as shown by the multiple linear ablation elements such as Figures 23A to 25 so that it can be directly advanced onto a surface facing it in a plane. This would be similar to the situation shown in Figure 20, but the orientation of the tube 2020 is closer to the perpendicular to the surface of the tissue 50. The angle of bending can be any selected angle, for example, between 0° and 90°. Optionally, the angle of bending is sharp (bending greater than 90°), which is a potential advantage for "reaching behind" - for example, to allow reaching tissue very close to the body cavity orifice where the plasma delivery tip is introduced, and / or to allow a greater range of maneuverability. The reorientation when advancing from a lumen is optionally applied to other embodiments where an electrode assembly can be advanced outside a lumen and thus delivered to a treatment site, such as Figures 19A to 19F or any one of 21A to 21B.

[0487] Figures 21A to 21B Another expandable electrode is shown: the expandable discharge electrode assembly 2120. In some embodiments, a conductive portion 2121 of the expandable discharge electrode assembly 2120 includes a superelastic alloy ring that is elastically prone to expansion, thereby opening its ring aperture 2121A. The conductive portion 2121 is optionally embedded within a shell layer 2122 of insulating material to form an insulating barrier.

[0488] When restricted by the tube 2010 (which can also be an ionized gas delivery tube), the ring of the conductive portion 2121 remains closed. Upon exiting the restriction of the tube 2010, the ring opens, having the effect of widening (and optionally also flattening) the surface area of the discharge electrode assembly 2120 on which the ionized gas can be converted into plasma. Withdrawing back into the tube 2010 squeezes the ring of the conductive portion 2121 to close again.

[0489] It should be noted that Figures 19A to 19FThe multiple extended shapes of the multiple discharge electrode assemblies undergo "assistive folding" due to the folding of the multiple extended cross-sectional shapes of the multiple tubes that surround them. The multiple discharge electrode assemblies of these figures can be advanced and / or retracted into their respective tubes freely from their respective tubes when those tubes themselves unfold into their extended shapes because the two shapes match sufficiently to allow it. Once retracted into their outer shell tubes, a discharge electrode assembly wider than the sheath that delivered it can be folded to its fully retractable state (and, for example, withdrawn from the body) by the folding force applied from the multiple tubes around it - because that tube itself is folded by withdrawing the sheath from which it emerged. In contrast, Figures 20A to 21B The multiple embodiments of include multiple discharge electrode assemblies that, while not circular themselves, can be advanced and retracted into multiple circular lumens having a diameter less than their own width when fully extended. These discharge electrode assemblies may be particularly suitable for use with the multiple circular working channels of a variety of other devices; for example, the multiple standard working channels of a colonoscope.

[0490] Now referring to Figures 22A to 22C which schematically shows a flow-diffusing electrode assembly 2220 for use with a plasma delivery tip 2201 according to some embodiments of the present invention.

[0491] In some embodiments, a shell layer 2022 of a discharge electrode assembly 2220 is provided with a flow-diffusing flange 2223 that substantially fills the lumen of the ionization gas delivery tube 2010 when the discharge electrode assembly 2220 is confined within the lumen of the ionization gas delivery tube 2010. Upon its initial advancement from the ionization gas delivery tube 2010, the flow-diffusing flange 2223 creates a relatively narrow orifice that redirects the ionization gas flow (indicated by arrow 2235) into a diffused configuration. The plasma 2230 generated by the discharge electrode 2221 in the ionization gas flow is also thereby distributed. As the flow-diffusing flange 2223 is advanced further, the degree of diffusion of the ionization gas flow 2236 decreases, resulting in a finer plasma plume 2231. By interconverting between these configurations (and optionally further advancing the flow-diffusing flange 2223), a circular area can be swept with plasma. If present, through multiple slight lateral offsets of the gas delivery tube 2010, plasma coverage can be provided to a "shadow" area directly in front of the discharge electrode assembly 2220. Such movement can occur naturally during the plasma treatment, for example due to multiple normal body movements, and / or be deliberately generated by the device operator.

[0492] It should be noted that the gap between the flange 2223 and the lumen wall of the tube 2010 can be circular or interrupted, for example, by further distally extending the flange 2223 in some places. Interrupting the gap can allow preferential guidance of the ionized gas flow, for example, in two opposite directions, so that the plasma plume cross-section has a longer axis and a shorter axis. This shape may be suitable for sweeping a target. For a similar total gas flow rate, compared with a circular hole, the concentration of the ionized gas flow through multiple smaller holes can concentrate and / or extend the plasma plume to reach a wider range along the longer axis.

[0493] Now refer to Figures 23A to 23B , which schematically shows an off-axis deployed discharge electrode assembly 2320 used with a plasma delivery tip 2301 according to some embodiments of the present invention.

[0494] In some embodiments, the discharge electrode assembly 2320 includes a superelastic electrical conductor (such as including nitinol) 2321, optionally within a sheath 2322 of an insulating material (such as a polymer coating) that acts as a dielectric barrier. When confined within the ionized gas delivery tube 2010, the discharge electrode assembly 2320 remains relatively straight. When emerging from a distal end of the ionized gas delivery tube 2010, the discharge electrode assembly 2320 presents a bend away from a central longitudinal axis of the ionized gas delivery tube 2010, for example, forming an angle of at least 45°, optionally up to about 70°, 80°, or 90° with the center. In some embodiments, the discharge electrode assembly 2320 projects far enough from the gas delivery tube 2010 such that it radially extends beyond the lumen cross-section of the gas delivery tube 2010; for example, radially extending more than a radius of the lumen cross-section from the central axis.

[0495] In some embodiments, the discharge electrode assembly 2320 bends more than 90°, for example, all the way back (proximally) behind the hole from which it emerges. This has potential advantages for reaching areas adjacent to a hole used for accessing a body cavity. To bring the ionized gas to the same area, the entire lumen can be filled with ionized gas, or the ionized gas can be diverted from a lateral hole, optionally, the lateral hole is provided with a partially backward (proximal) angle.

[0496] One option for holding the discharge electrode in the gas flow is to position the ionized gas outlet hole of the tube 2010 close enough to the surface of the tissue 50 including the treatment target 51 such that the gas flow (e.g., as Figure 23BThe one shown by arrow 2331 therein is laterally deflected. In a sufficiently enclosed lumen space, once the ionized gas diffuses sufficiently therein, it may not be necessary to reorient the gas flow. When an appropriate voltage is delivered from the electrical conduit 2323 to the discharge electrode assembly 2320 along the conductor 2324, multiple portions of the ionized gas flow passing along the discharge electrode assembly 2320 can then be ionized. As a result, a linearly extending contact area can be generated between the plasma plume 2330 and the adjacent tissue. Multiple linear scanning movements of the tube 2010 transverse to the axial extent of the discharge electrode assembly 2320 can be used to produce coverage over a wider surface area.

[0497] Optionally, the shape of the discharge electrode assembly 2320 has a curvature to match its target. For example, an inwardly protruding treatment target 51 (such as a raised area of cancerous tissue) can be accommodated by shaping the discharge electrode assembly 2320 to have a concave surface 2325. Additionally or alternatively, multiple straight and / or convex shapes can be provided.

[0498] Now refer to Figures 24A to 24C , which schematically shows an off-axis deployed electrode assembly 2420 used with a plasma delivery tip 2401 having an off-axis oriented ionized gas exit hole 2416 according to some embodiments of the present invention.

[0499] In some embodiments, the ionized gas flow 2431 is reoriented off-axis to match the off-axis positioning of a discharge electrode assembly 2420. In the example shown, a cap 2415 has an off-axis hole 2416 on its side. The placement of the side of the hole 2416 helps to reorient the ionized gas flow along the discharge electrode assembly 2420 (which optionally also exits the tube 2010 through the hole 2416).

[0500] The cap 2415 can be fixed in place at a distal side of the tube 2010 ( Figure 24C ). Alternatively, it can be attached to a more proximal portion of the discharge electrode assembly 2420 ( Figure 24C ), such that the two are advanced distally together. Figure 24C A potential advantage of the construction of Figure 24C is its suitability for use with a multi-purpose working channel. The attachment of the cap 2415 to the discharge electrode assembly 2420 allows it to be completely withdrawn from the working channel during a procedure, thus freeing the working channel for multiple other uses that a procedure may require. Another potential advantage is avoiding having to pass the discharge electrode assembly 2420 through the narrow hole 2416 provided by the cap 2416, although this can be mitigated, for example, by providing multiple tapered inner surfaces as guides. In cases where no reconfiguration of the working channel is required,

[0501] In some embodiments, the discharge electrode assembly 2420 can rotate freely relative to the aperture 2416, at least within the multiple limitations allowed by the dimensions of the aperture. Optionally, this is used as a method of power regulation. When the discharge electrode assembly 2420 is maximally located within the ionized gas flow exiting the aperture 2416, the ionization region is the longest. A corresponding maximum plasma may be generated - but more heat may also be generated. In some embodiments, rotating the discharge electrode assembly 2420 partially out of the gas flow reduces the amount of dissipated power. Optionally, this is used as a method of power regulation (and corresponding temperature regulation). It is noted that due to the multiple non-linearities in the multiple mechanisms controlling plasma generation, the multiple electrical control parameters (such as voltage) controlling power delivery may not be easily adjustable. For example, below a certain threshold voltage, plasma generation may suddenly stop.

[0502] Now briefly refer to Figure 25 , which schematically shows an off-axis deployed discharge electrode assembly 2520 for use with a plasma delivery tip 2501 according to some embodiments of the present invention. For example, compared to the discharge electrode assembly shown in Figures 23A to 24C , the discharge electrode assembly 2520 includes a convex surface 2525, which may be more suitable for introducing the plasma plume 2532 into a tissue concave surface, such as a concave surface that may otherwise partially obscure a treatment target 51. It should be understood that the discharge electrode assembly 2520 can be introduced while being restricted within the tube 2010, extended for plasma treatment to the shown configuration, and then withdrawn back into the tube 2010 again to prepare for withdrawal from the treatment area. In some embodiments, the discharge electrode assembly 2520 can rotate about a longitudinal axis of the tube 2010, optionally together with the cap 2415. This can allow, for example, area coverage while the tube 2010 remains in a single position.

[0503] Now briefly refer to Figure 26 , which schematically shows a self-expanding discharge electrode assembly 2620 for use with a plasma delivery tip 2601 according to some embodiments of the present invention.

[0504] In the shown example, the inflection of the discharge electrode assembly 2620 (i.e., a first curve in a radially outward direction, followed by a second curve in a radially inward direction) allows for providing a longitudinal range of an extended plasma generation electrode, which remains generally centered on the longitudinal proximal-to-distal axis of the tube 2010. Centering the discharge electrode assembly 2620 may increase the amount of the ionized gas flow (arrow 2631) available for generating the plasma plume 2632. The curvature of the discharge electrode assembly 2620 along which plasma is generated can be convex and / or concave relative to the tissue as shown, for example with respect to Figures 23A to 24Cas described. The discharge electrode assembly 2620 can be alternately extended from and retracted into the tube 2020, e.g., as described with respect to Figure 25 and in multiple other figures herein.

[0505] In some embodiments, the discharge electrode assembly 2620 can rotate about a longitudinal axis of the tube 2010. This can allow, for example, area coverage while the tube 2010 remains in a single position.

[0506] Optionally, the discharge electrode assembly 2620 unfolds from a lumen that is not itself a gas delivery tube. Optionally, the gas delivery tube is separate from or disposed side-by-side with the discharge electrode assembly 2620. In some embodiments, a distal end of the discharge electrode assembly 2620 is formed as a ring, and the gas delivery tube is circumferentially disposed within the ring.

[0507] Now refer to Figures 27A to 27B , which schematically shows a self-expanding discharge electrode assembly 2720 for use with a plasma delivery tip 2701 in accordance with some embodiments of the present invention. Also refer to Figures 28A to 28C , which schematically shows a plasma delivery tip 2801 that encapsulates the self-expanding discharge electrode assembly 2720 differently than shown in Figures 27A to 27B .

[0508] In these examples, the discharge electrode assembly 2720 includes a plurality of flexible members 2727, each flexible member 2727 extending away from a central member 2726 to which the plurality of flexible members 2727 are connected. For example, flexibility and elasticity are imparted by forming the conductive elements 2721 of the discharge electrode assembly 2720 using a superelastic alloy. Optionally, an insulating sheath 2722 is provided as an electrical resistance barrier.

[0509] As Figure 27A shown, folded and confined within the tube 2010, the plurality of flexible members 2727 can deflect distally to allow them to fit within the lumen of the tube 2010. After being unconfined, the plurality of flexible members 2727 self-expand by bending proximally and radially outward from a central longitudinal axis of a distal portion of the tube 2010 to assume their expanded configuration. In the example shown, these members expand to present a convex surface toward the processing target 51. It can be understood that a straight or concave surface is alternatively or additionally presented toward the processing target 51, e.g., as described with respect to Figures 23A to 24C .

[0510] As an alternative to the packaging shown in Figure 27A , the plurality of members 2727 (in Figures 28A to 28CFurther differentiated into members 2727A and 2727B in ) can be restricted such that at least one of them is placed on the axis of the central member 2726. In Figures 28A to 28C a control member 2841 is provided, which can be used to assist in the refolding of the discharge electrode assembly 2720 to allow it to be retracted. Applying tension to the control member 2841 pulls the member 2727A towards the distal hole of the tube 2010 ( Figure 28B ), such that the discharge electrode assembly 2720 can be retracted into the tube 2010 ( Figure 28C ), including the trailing member 2727B which can be deflected to enter the lumen of the tube 2010. Optionally, the control member 2841 also serves as an electrical conduit for transmitting the discharge voltage to the discharge electrode assembly 2720.

[0511] In some embodiments, the discharge electrode assembly 2720 can rotate about a longitudinal axis of the tube 2010. This can allow, for example, area coverage when the tube 2010 is held in a single position.

[0512] Multiple adjustable direction plasma tips

[0513] Now refer to Figures 20A to 20C , which schematically shows a

[0514] Now make an introductory reference to Figures 29A to 50 regarding some of the multiple specific combinations that can be made between the multiple features described in multiple different examples for this document.

[0515] For the sake of brevity and clarity of description, except for the specific features or multiple features provided by the multiple examples to illustrate, Figures 29A to 50 examples of many of the multiple embodiments in are generally represented (for example, without specifically indicating the power supply conduit and / or multiple discharge electrodes).

[0516] For example, in any of these figures, the multiple gas supply tubes marked with multiple reference numerals within the range 119A to 119Z should also be understood as multiple examples of a more general gas supply tube.

[0517] Some of these gas supply tubes (for example, those described with respect to Figures 32A to 39 , 46A to 46B, 48 and / or 50) are of the type of the gas supply tube 603, which is provided with a separate discharge electrode assembly 601 (when such an assembly is shown). For multiple embodiments of this type, multiple designs (for example, multiple designs of the discharge electrode assembly 601 itself) and multiple principles are described, for example, with respect to Figures 6A to 12B, 13F, 14C, 19A to 19F and / or 20A to 28C may optionally be combined with the multiple additional features described with respect to the particular gas supply tube, its associated discharge electrode assembly or assemblies, and / or the multiple examples associated therewith as a whole.

[0518] Multiple other embodiments (such as those described with respect to Figures 29A to 29B , 31A to 31C, 40A to 43, 45A to 45B, 47A to 47C and / or 49) are of the type in which the discharge electrode is circumferentially positioned around a lumen space defined by the gas supply tube and / or its outlet orifice. For multiple embodiments of this type, multiple designs and multiple principles are described, such as those with respect to Figures 1B to 5D , 13A to 13E, 14B, 15A to 15C and / or 17A to 18D may optionally be combined with the multiple additional details described with respect to the particular gas supply tube and / or the multiple examples associated therewith as a whole.

[0519] Figures 29A to 50 Several of the multiple figures of Figure 11A and 11C include an indication of a working channel 115, shown as a simple lumen, which may be provided, for example, by a catheter. However, it should be understood that in any of these examples, the working channel 115 may be a channel of any device having an extended lumen adapted to receive a gas supply tube therethrough, such as an endoscope (such as a gastroscope, arthroscope and / or colonoscope). Thus, for example, the working channel 115 may be one of multiple channels configured together, for example, within a single probe body of a colonoscope. The working channel 115 may be provided separately from a plasma delivery device passing through the working channel 115.

[0520] In addition, with respect to Figures 29A to 50 the multiple plasma delivery tip examples described generally do not require the use of a working channel 115. They may be introduced separately into the site of their operation or, alternatively, positioned there, for example, by using forceps.

[0521] Figures 29A to 50 Several of the multiple figures of

[0522] Just described with respect to Figures 29A to 50The multiple comments above should not be construed as excluding any combinations not mentioned by omission. For example, in some embodiments, the multiple principles described extend to multiple combinations of multiple features described with respect to the multiple figures herein, which may not include Figures 29A to 50 any of them.

[0523] Now refer to Figures 29A to 29B , which schematically shows multiple plasma delivery tips delivered through a working channel 115 within a sleeve 117 according to some embodiments of the present invention.

[0524] The gas supply pipes 119A, 119B are respectively an example of a gas supply pipe. For clarity, they are generally shown (e.g., without specifically indicating the power supply conduits and / or the multiple discharge electrodes) except for the positioning of their respective gas (and / or plasma) outlet holes 120A, 120B. In some embodiments, multiple plasma delivery tips are implemented in the region of the outlet hole 120A (a distally facing hole) according to any one of the multiple configurations such as Figures 1B to 5D . In some embodiments, multiple laterally facing outlet holes 120B are optionally implemented, such as as described with respect to Figures 13A to 13E . The plasma plumes 10, 10A, 10B are also indicated.

[0525] A main difference between a sleeve 117 and a working channel 115 is that the working channel 115 can be provided separately, while the sleeve 117 is considered part of the plasma delivery device.

[0526] In addition to this, when both are provided, there is an optional functional division between them. The working channel 115 helps to position multiple tools (in this case the plasma delivery tips) in place. It is typically provided on a device that provides the stiffness and maneuverability suitable for reaching, for example, a treatment site. Then, the working channel lumen becomes a relatively low resistance path along which other multiple devices, such as a plasma delivery tip, can also be brought to the treatment site.

[0527] The sleeve 117 provides protection for the plasma delivery tip itself, such as mechanically isolating the plasma delivery tip when the plasma delivery tip passes through the working channel 115. This potentially enhances the pushability, especially in cases of embodiments where the plasma delivery tip is divided into multiple smaller and potentially more delicate multiple channels (e.g., as in Figures 36A to 50 ), and / or in cases of embodiments that include multiple elements that are elastically inclined to form an angle by themselves (e.g., Figures 31A to 33C ), which may resist advancement through a working channel if not encapsulated.

[0528] In some embodiments, the sleeve 117 includes a dielectric material (e.g., a polymer) that is additionally used to increase electrical isolation and / or reduce the external surface inductance of the voltage supplied from the environment to a plasma delivery tip. This can prevent accidental plasma discharges in the case where the ionized gas leaks back along the working channel. Additionally, it can itself help prevent such leakage by filling a portion of the working channel volume not filled by the gas delivery tube itself. Alternatively, the ionized gas exhausted through a conduit is mixed with a gas having a higher breakdown voltage (e.g., through a mixture in the plasma generation environment and / or by direct supply to the exhaust conduit itself). This also potentially helps prevent off-site plasma generation along the exhaust conduit.

[0529] The sleeve 117 can also help center the plasma delivery tip. The sleeve 117 can be used to support and / or protect multiple electrical connections to a plasma delivery tip used in power delivery and / or sensing (e.g., Figure 3A the sheath 101 of which surrounds most of the length of multiple electrical conduits 105). While separating these functions into multiple separate tubes has some potential advantages (e.g., allowing the same working channel to be used for one or more purposes during a procedure other than plasma delivery), it should be understood that the multiple functions separately described for the working channel 115 and the sleeve 117 can optionally be combined into a single tube, particularly for multiple embodiments where the working channel 115 does not need to be cleared during a procedure for use with multiple other tools.

[0530] Figures 29A to 29B Multiple aspects of plasma delivery related to the following are reintroduced:

[0531] · Providing multiple plasma generation sites (e.g., as also described with respect to Figure 13E ),

[0532] · Directing the multiple added plasma plumes to multiple positions that complement each other appropriately (e.g., as also described with respect to Figures 13A to 13F and / or 14A to 14C),

[0533] · "Scanning" the multiple plasma plumes to cover a larger area than the cross-section provided by the plume itself (e.g., as also described with respect to Figure 3A and / or 14A to 14C).

[0534] These features point to multiple ways of addressing the problem of matching the plume size to the target size. The problem arises in part due to miniaturization reducing the size of a plasma delivery tip to a diameter of 2 to 20 mm (typically), suitable for use within a body cavity.

[0535] The problem is also related to the practical problem that for any specific geometry of a plasma delivery tip, in practice the plasma may only be verified for use within a relatively narrow range of plasma generation parameters, and in particular a range that includes a relatively narrow range of plasma plume diameters. Outside of this range, plasma generation may not occur reliably (or at all); or it may occur, but the generation of potentially therapeutic plasma species is unknown or insufficient. Generally, simply scaling up a small plasma generation tip to a larger one results in such a large change in the plasma generation characteristics that it must be effectively re-verified as a new design.

[0536] Thus, for example, where the plasma exits from a round-hole delivery tube, the plasma plumes made of the jet gas tend to be pencil-shaped. For example, Figure 29A the shape of the plasma plume 10. This shape is a result of many factors, such as: the parameters of the ionized gas, the parameters of the ionized gas flow, the electrical parameters in the plasma for generating the initial ionized species, the geometric parameters such as the shape of the electrode and the plasma exit hole, and the gas flow and / or electrical interaction of the plasma plume with its environment. The shown plume shape is an "unconstrained" shape, such as the shape that a plasma plume might assume in an open-air environment. However, the shape also changes depending on how the gas and / or current are affected by the proximity of other surfaces (such as a treated surface). Optionally, this is also considered an important parameter when validating a plasma plume for delivering ionized species to a target such as an abnormal tissue area.

[0537] Once the use of the plasma plume has been verified (e.g., as Figure 29A shown, and / or as described with respect to other figures herein, e.g., Figures 17A - 28C ), in some embodiments, even if the geometry of the plasma plume may not be optimal for each target - for example, the pencil shape as Figure 29A shown - it may be preferable to limit the operation to using the parameters that generated it (optionally allowing parameter adjustment within a range of acceptable values).

[0538] Adding multiple plasma plumes, controlling the direction of these plasma plumes, and / or scanning these plasma plumes by moving them over a target area are all potential ways to overcome the limitations imposed by such practical considerations. The same selected plasma generation parameters can be replicated at multiple exit holes to similarly produce a plasma plume at each, and then all of these plasma plumes can be combined to deliver plasma to a target area. Additionally or alternatively, the plasma plumes can be moved over a target area, helping to ensure that it receives sufficient coverage.

[0539] For example: For a distally-directed plasma plume 10B, Figure 29B the example of also adds a plurality of laterally-directed plumes 10A. In the example shown, these plumes are oriented substantially perpendicular to the plasma plume 10B. This configuration can be used to increase the area near the plasma delivery tip that the plasma reaches because (1) there are more plasma plumes, (2) the plurality of plasma plumes cover more directions, and (3) the gas delivery tube 119A is optionally rotated (double arrow 2904) such that the plurality of laterally-directed plasma plumes 120A sweep through an approximately cylindrical area.

[0540] The sleeve 117 is optionally a tube that extends all the way back to the proximal end of the device (e.g., to the handle 80 and its various controls). Alternatively, the tubular portion of the sleeve 117 can be restricted to only a distal region of a plurality of structures that include only the plasma delivery tip (a "partial length" embodiment of the sleeve 117). These structures are optionally held inactive when needed, for example, using a control member that extends proximally to the handle 80. Optionally, the working channel itself is fitted with a fixed lug that slightly narrows the working channel bore (e.g., tapers gradually along a taper) to a diameter that still allows the structures of the plasma delivery tip to be advanced therethrough while keeping the sleeve 117 itself in place. A potential advantage of the partial length embodiments of the sleeve 117 is that the gas delivery tube itself can be widened, which can reduce the resistance to the ionized gas flow and / or provide more space for a plurality of electrical connections.

[0541] Now refer to Figures 30A to 30B , which schematically depicts a mode of plasma interaction with a surface according to some embodiments of the present invention, the surface being generated by rotating a longitudinal axis that is offset and / or tilted from a longitudinal axis of the plasma plume itself about the longitudinal axis of the plasma plume. Also refer to Figures 31A to 31C , which schematically depicts a self-orienting plasma delivery tip 3101 according to some embodiments of the present invention, which can be actuated to reorient a plasma outlet hole 120A through a range of off-axis orientations relative to a longitudinal axis 13 of the sleeve 117 and / or the working channel 115 that delivers it.

[0542] In Figures 31A to 31C the example, the gas supply tube 119c is configured with a closed distal end and a side outlet hole 120A near the distal end. In addition, a section of the distal end of the gas supply tube 119C is preconfigured to assume an angled shape when unrestricted (e.g., as shown in Figure 31C ), while having sufficient flexibility to straighten when it is retracted into the sleeve 117. For example, the gas supply tube 119C can include a superelastic alloy such as Nitinol, allowing it to convert between the straightened shape and the angled shape.

[0543] exist Figure 31A In the partially deployed case, plasma plume 10C is oriented generally transversely from a longitudinal axis defined by the distal end of sleeve 117 and / or working channel 115. This may be useful for striking surfaces substantially perpendicular to surface 11, but in the example shown, surface 11 is considered the target - for example it may be a tissue surface of an area having abnormal tissue.

[0544] Extending the gas supply tube 119C further from the sleeve 117 allows the gas supply tube 119C to assume a partial bend. The exit hole 120A is now oriented obliquely to the surface 11 so that the plasma plume 10C can impact it. In this example, the region of impact extends within the region 14A, which also happens to include the place where the imaginary longitudinal axis 13 (a central longitudinal axis of the sleeve 117) intersects the surface 11.

[0545] When viewing the surface 11 from a vertical angle ( Figure 30A ), region 14A is decomposed into an approximately elliptical region. Gas delivery tube 119C can also rotate around axis 13 (as shown by double arrow 3004). When it rotates, plasma plume 10C sweeps out an approximately circular region 3002.

[0546] exist Figure 30B , the gas delivery tube 119C is further extended so that it finally assumes its predetermined angle - in this case, an angle of about 90° with the axis 13. The final predetermined angle can be any suitable angle, for example, an angle between about 45° and 90°; or an angle greater than 90°, such as up to about 135°, and / or less than 45°, such as about 30°. In this figure, the plasma plume 10C also strikes the surface 11 at an angle of about 90°. This causes the plasma to strike a roughly circular area 14B on the surface 11, such as Figure 30B Since circle 14B does not include the intersection of axis 13 and surface 11, when rotated in the direction indicated by double-headed arrow 3014, the resulting rotated shape has a hole 3015 at its center.

[0547] In some embodiments, complete coverage of a target area is generated by advancing the gas delivery tube 119C to one or more of its multiple partially or fully bent positions and rotating it in a circular motion. Figure 3B and 31C The central area as a "dead spot" (untreated) can be used Figure 31B The structure is reached by Figure 31B The construction of the process area omits or only weakly processes multiple edges of the process area. Figure 31C The structure is processed.

[0548] A potential advantage of using a circular scanning motion is that it can be easily controlled by rotating a control element located proximal to the working channel 115 and in semi-rigid torque communication with the distal end of the gas delivery tube 119C. A complete rotation (or more than one rotation) can be easily determined. Figures 31A to 31C The transition between the multiple states can also be easily determined, for example, by the distance of the longitudinal translation of the same or another proximally located control element.

[0549] It should be noted that the area of the impact can also be changed by advancing the entire plasma delivery tip 3101 closer to or farther from the surface 11.

[0550] Now refer to Figures 32A to 32C , which schematically shows a self-orienting plasma delivery tip 3201 according to some embodiments of the present invention, which can be actuated to reorient a plasma exit hole 120A through a range of multiple off-axis orientations relative to the sleeve 117 and / or the longitudinal axis 13 of the working channel 115 through which it is delivered. The example shown uses a discharge electrode assembly 601 connected to power through an electrical conduit 105; alternatively, a circumferential electrode configuration is used.

[0551] The gas supply tube 119D is configured to transition from straight to some predetermined maximum bend, as also described for the gas supply tube 119C.

[0552] Since the exit hole 120A is orthogonal to the axis 13, when the gas supply tube 119D is minimally extended, the plasma plume 10D impinges orthogonally on the surface 11 ( Figure 32A ), and the axis 13 itself is orthogonal to the surface 11. This results in an approximately circular area of plasma impingement 14C that is almost the same as the area that would be swept out if the gas supply tube 119D were rotated about the axis 13.

[0553] Partial advancement of the gas supply tube 119D ( Figure 32B ) results in an inclined intersection angle between the plasma plume 10D and the surface 11, and the rotation (double arrow 3215) of the area of static plasma impingement 14D allows an approximately circular area to be swept out; again with a central "dead zone" that can be filled by multiple sweeps in a smaller extended configuration.

[0554] In this example, full extension of the gas supply tube 119D causes the plasma plume 10D to point parallel to (and not impinge on) the surface 11. This can be useful, for example, for laterally directing the plasma to a surface that extends substantially parallel to the longitudinal axis 13. In this regard, it should be noted Figures 31A to 33CThe ranges of the multiple transition angles and rotation angles shown in [the figure] can also be used to process a substantially cylindrical region while the sleeve 117 and / or the working channel 115 remain stationary, thereby obtaining multiple potential advantages similar to the multiple coverage controls of a circular region of the surface 11.

[0555] Now refer to Figures 33A to 33C , which schematically shows a self - orienting plasma delivery tip 3301 according to some embodiments of the present invention, which can be actuated to re - orient a plasma outlet hole 120C through a range of multiple off - axis orientations relative to a longitudinal axis 13 of the sleeve 117 and / or the working channel 115 that delivers it. The configuration in this example is similar to Figures 32A to 32C the configuration in [the reference], except that a hood 114 is added, which is used to deflect the plasma plume 10E onto an axis inclined to the axis 13 even when the gas supply tube 119E is almost completely retracted into the sleeve 117. This can make a wider range of multiple deployment angles useful for plasma delivery (for example, there is no complete miss of the deployment angle pointing to the surface 11 in the direction, so some impact regions 14E, 14F, 14G are shown within the entire range of angles assumed by the gas supply tube 119E). When rotationally swept (double - arrow 3315), this example allows the small dead zone around the intersection of the axis 13 and the surface 11 to be converted by a slight offset or wobble of the working channel 115; or this can be avoided by providing a smaller deflection, so that the impact regions of most of the withdrawn configurations include the intersection of the axis 13 and the surface 11. Figure 13B Shows another tip configuration capable of producing an angled outlet hole.

[0556] Multiple plasma tips composed of multiple plasma generation sites

[0557] Now refer to Figures 34A to 34B , which schematically shows a plasma delivery tip 3405 provided with multiple discharge electrode assemblies 601 according to some embodiments of the present invention. Also refer to Figure 35 , which shows the Figures 34A to 34B plasma delivery tip 3405 operating in a manipulable configuration according to some embodiments of the present invention.

[0558] One of the multiple potential problems of making the cross - section of a plasma plume larger is that the electric - field gradient decreases significantly with the distance from the discharge electrode, so even if the cross - section of the gas supply tube is large, plasma generation is concentrated around the discharge electrode. In Figure 34AIn the said example, a plurality of discharge electrode assemblies 601 are provided, and a similar air flow can be generated around each of the plurality of discharge electrode assemblies 601 by flowing through the gas supply lumen 119Q. Each of the plurality of discharge electrode assemblies 601 is powered, resulting in a plasma plume 10F that is a superposition of substantially several individually generated plasma plumes.

[0559] In Figure 34A , the plurality of discharge electrode assemblies 601 partially extend from the gas supply pipe 119Q; they can alternatively or additionally be held within the gas supply pipe 119Q. Their relative spacing is optionally maintained by separating them with a spacer and / or by connecting them together to form one or more multi-headed "branch candelabra" discharge electrode assemblies. Figure 34A Four discharge electrode assemblies 601 are shown; alternatively, another number can be provided, for example, 2, 3, 4, 5, 6, 7 or more discharge electrode assemblies. Optionally, the plurality of discharge electrode assemblies 601 are electrically separated from each other, for example, separately or separated into multiple groups. The plurality of separated electrodes are optionally powered simultaneously (e.g., from multiple different power sources), or powered in a rapidly rotating manner, such as using a multiplexed or phase-shifted pulse wave modulation method. Delivering power to multiple different discharge electrodes separately in time may help reduce the multiple non-linear interactions between multiple different plasma generation sites.

[0560] Optionally, each discharge electrode assembly 601 is connected to electrical power through a flexible conductive member 3401, which is preconfigured to assume an angled configuration when leaving the confinement of the gas delivery pipe 119Q. In some embodiments, the bending of these flexible conductive members 3401 as they extend displaces the plurality of discharge electrode assemblies 601 away from the central axis of the gas supply pipe 119Q. Optionally, they are displaced into a substantially flat region, and the distance between multiple pairs of the most widely spaced discharge electrode assemblies is greater than the lumen diameter of the gas supply pipe 119Q. To place the plurality of dispersed discharge electrode assemblies 601 into the ionized gas flow, the gas supply pipe 119Q is positioned close enough to a target surface 11 to force the confined ionized gas flow to diffuse laterally.

[0561] Then, the plurality of discharge electrode assemblies 601 can be advanced into the region of the air flow to generate a plasma plume; for example, plasma plume 10N. In a sufficiently enclosed lumen space, once the ionized gas has diffused sufficiently therein, it may not be necessary to redirect the air flow. Optionally, the plurality of discharge electrode assemblies 601 can rotate together (as shown by the double-headed arrow 3405) to make the plasma contact the surface 11 evenly. The rotation can be performed, for example, by the rotation of an electrical conduit to which each of the plurality of conductive members 3401 is connected, and / or by the rotation of the gas supply pipe 119Q.

[0562] When multiple discharge electrode assemblies 601 are in Figures 34A to 34B any suitable intermediate position between the positions shown, a plasma plume may optionally be generated.

[0563] Figure 35 Shown is the superposition of three different bending states of the gas supply tube 119Q, which is optionally configured to be bendable controllably; for example as described with respect to Figure 3A and / or 14A. This can be used in particular to treat multiple large areas of a curved lumen wall surface 11A, such as may be present, for example, inside a bladder.

[0564] Now refer to Figures 36A to 36B , which schematically shows a plasma delivery tip 3601 provided with multiple discharge electrode assemblies 601 according to some embodiments of the present invention, the multiple discharge electrode assemblies being operable with a corresponding plurality of separate gas supply tubes 119J.

[0565] In Figure 36A , the plurality of separate gas supply tubes 119J are kept fully accommodated within the sleeve 117, where the multiple discharge electrode assemblies 601 project. Optionally, the multiple discharge electrode assemblies 601 can be fully retracted into the sleeve 117 and / or the multiple gas supply tubes 119J.

[0566] In Figure 36B , the multiple gas supply tubes 119J have been partially advanced from the sleeve 117. This is another way to generate a combined plasma plume, such as the plasma plume 10F described with respect to Figure 34A .

[0567] A potential advantage of this more fully personalized embodiment is greater isolation (and thus independence) between the multiple plasma generation sites. Optionally, they can be operated with multiple separate gas flows and / or separate electrical powers, or in combination. This potentially allows for individual adjustment of multiple plasma generation parameters for each plasma generation unit (each "unit" comprising one of the plurality of gas supply tubes 119J and one of the plurality of discharge electrode assemblies 601). Crosstalk between the multiple plasma generation units can also be reduced, so that when multiple such units are combined, the multiple plasma generation parameters developed for a single unit are less likely to need adjustment. Multiple other things that can be done with multiple separate plasma generation units are described with respect to Figures 40A to 41 ; for example, the multiple distal ends of each gas supply tube 119J can be configured to rearrange into a larger (more dispersed) pattern as they are advanced from confinement, and / or rearrange into a different shaped (e.g., linear) pattern as they are advanced from confinement.

[0568] Now refer toFigure 37 and 39 , which schematically shows a plasma delivery tip 3701 provided with a plurality of discharge electrode assemblies 601 according to some embodiments of the present invention, the plurality of discharge electrode assemblies 601 being operable with a corresponding plurality of individual gas supply tubes 119F that expand into a radially expanding shape when advanced from a confinement. This embodiment can be regarded as Figures 34A to 35 a combination of multiple features of Figures 36A to 36B and multiple features of Figure 37 . Each discharge electrode assembly 601 retains its own gas supply tube 119F instead of diffusing into a common "cloud" of ionized gas, which may help to maintain more stable plasma generation conditions at each site and better ensure the independent operation of each plasma generation unit. In

[0569] Also as described in the example regarding Figure 34A , the plurality of discharge electrode assemblies 601 are optionally electrically combined together or electrically separated from each other, such as individually separated or separated into multiple groups. The multiple separated electrodes are optionally powered simultaneously (e.g., from multiple different power sources) or in a rapidly rotating manner, such as using a multiplexed or phase-shifted pulse wave modulation method. Delivering power to multiple different discharge electrodes separately in time may help to reduce the multiple non-linear interactions between multiple different plasma generation sites.

[0570] Figure 39 The plasma delivery tip 3901 of

[0571] Now referring to Figure 38, which schematically shows a plasma delivery tip 3801 provided with a plurality of discharge electrode assemblies 601 operable with a corresponding plurality of separate gas supply tubes 119H arranged linearly and branching from a common lumen of the gas supply tube 117A. Three tubes are shown; other numbers of the separate gas supply tubes 119H are optionally provided, such as 2, 4, 5, 6, 7 or more separate gas supply tubes 119H. A potential advantage of separation from a common lumen to the distal end is reduced complexity of the device at more proximal locations. There may also be, for example, reduced gas flow resistance, and / or more space available for electrical interconnections. As also described with respect to other embodiments described herein, ultimately separating the gas supply into separate lumens is a potential advantage for providing a larger plasma delivery area using plasma generation parameters determined for a small cross-section device.

[0572] Reference now Figures 40A to 40C , which schematically shows a manifold plasma delivery tip 4001 according to some embodiments of the present invention. The plasma delivery tip 4001 includes a plurality of gas supply tubes 119K, which can be deployed from a lumen confined in a sleeve 117 and / or working channel 115. In addition, (such as Figure 40B and 40C The plurality of gas supply tubes 119K are configured to bend slightly as they advance from confinement to a wider region of diffusion (e.g., they are bent when unconfined and forced together into a plurality of straighter configurations when confined). Figure 40C ), the multiple individually generated plasma plumes 10G together impact a larger area of ​​the surface 11 than they would from multiple locations where they are still confined.

[0573] Reference now Figure 41 , which schematically shows another manifold plasma delivery tip 4101 according to some embodiments of the present invention. In this example, the plurality of individual gas supply tubes 119L are configured to assume a substantially linear arrangement when deployed. This may be at least in part because the plurality of gas supply tubes 119L are bent so that they self-arrange into a linear form. Optionally, a truss 4110 is provided that has a preferred overall linear shape when unrestrained, but has sufficient flexibility and slack to fold over on itself when restrained by retracting the plurality of gas supply tubes 119L into the sleeve 117 and / or working channel 115.

[0574] Reference now Figures 42 to 43 , which schematically shows additional manifold plasma delivery tips 4201, 4301 according to some embodiments of the present invention. Figure 42In the example described above, at least some of the plurality of individual gas supply tubes 119M are provided with a plurality of lateral outlets 120A, from which a plurality of plasma plumes 10J are provided. The plurality of plasma plumes are oriented in a plurality of different directions, providing an approximately annular region of plasma coverage that can be scanned by rotation and / or longitudinal translation of the plurality of gas supply tubes 119M. Figure 43 Shows a plurality of angled outlet holes 120D of a plurality of gas supply tubes 119N. The plurality of angles of the plurality of outlet holes can be mixed; for example, the outlet of one of the plurality of gas supply tubes 119N is oriented to emit a plasma plume 10P directly along a longitudinal axis of a distal portion of the sleeve 117 and / or the working channel 115. This illustrates another way of generating a plasma plume, the distribution of such plasma plumes being wider than the diameter of the lumen used to deliver the plasma delivery tip. As another example of a plurality of mixed aperture orientations: In some embodiments, as Figure 42 shown in Figure 43 around the plurality of gas supply tubes 119N described above, another ring of a plurality of gas supply tubes is added, which is configured with a plurality of lateral outlet holes 120A as Figure 42 shown.

[0575] Now refer to Figures 44 to 46B , which schematically shows a plurality of embodiments of a plurality of self-rotating plasma delivery tips 4401, 4605 according to some embodiments of the present invention. The plurality of jets of ionized gas used to generate the plasma plumes 10L, 10M can provide a large amount of thrust. Several liters of ionized gas per minute (for example, equivalent to about 0.5 to 10 liters of atmospheric pressure gas per minute) can be ejected through a plurality of holes having a diameter less than about (for example) 1 mm, 2 mm or 3 mm. In some embodiments, this thrust is used by terminating the gas delivery tube 119P in a rotatably mounted cap 4410, which redirects the gas into a plurality of arms 4411, the plurality of arms 4411 themselves being oriented such that the gas exiting them causes a component of tangential thrust that causes the cap 4410 and the plurality of arms 4411 to rotate.

[0576] In Figure 44 , the plurality of arms 4411 are shown as being folded by a restriction within the sleeve 117. When advancing from the restriction ( Figures 45A to 45B and 46A to 46B), the plurality of arms 4411 extend radially (optionally beyond the diameter of the lumen less the sleeve 117), and their outlets are oriented such that at least a component of their plasma is tangentially oriented. This results in a circular motion of the plurality of arms 4411, as shown by the arrows 4601, 4501. The circular motion causes the plasma plumes 10L, 10M to distribute plasma circumferentially.

[0577] Figures 45A to 45BShows an example of using a plurality of circumferential electrodes within the plurality of lumens of the plurality of arms 4411. Figures 46A to 46B Shows an example of using a discharge electrode assembly that can be positioned within or outside the plurality of lumens of the plurality of arms 4411 within the ionized gas flow. Figure 45B And 46A is an end view of the plasma delivery tip, while Figures 45A to 45B provides a side view.

[0578] Although the plurality of orientations of the plurality of outlets of the plurality of arms 4411 provide a component of tangential orientation thrust for the plasma plumes 10L, 10M, they are also oriented such that the activities of the plasma plumes 10L, 10M extend (distally to the plurality of arms 4411) some in front of the plurality of arms 4411, thereby allowing treatment of a surface that is also distally in front of the plurality of arms 4411. Alternatively, the plurality of outlets of the plurality of arms 4411 are oriented parallel to the longitudinal axis of the distal portion of the sleeve 117 and / or the working channel 115, or even oriented to direct the plasma slightly proximally. In this and other embodiments herein (e.g., Figures 31A to 33C exemplary embodiments), a plurality of proximally oriented plasma plumes can be provided to allow treatment of tissue located near an integrated lumen into which the device has been introduced.

[0579] Now refer to Figures 47A to 48 , which schematically shows alternative embodiments of the internal components of a plurality of self-rotating plasma delivery tips 4401, 4605 according to some embodiments of the present invention. These figures focus on various methods of transmitting (or avoiding transmission) of electrical power through the rotary connection 4705 formed by the cap 4710 and the gas delivery tube 119P.

[0580] In Figure 47A , the lead of the electrical conduit 105 terminates at the discharge electrode 4712, which is located proximal to the connection 4705. Therefore, there is no need to transmit electrical power through a sliding electrical connection. However, the plasma range may be reduced because it has to travel further before reaching the plurality of outlets of the plurality of arms 4411.

[0581] Figure 47B , 47CThe multiple embodiments of FIGS. 47 and 48 both use a sliding brush type arrangement to transfer electrical power through the rotary connection 4705. The electrical conduit 105 terminates at one or a set of contacts 4723 on the side of the gas supply conduit 119P, and the contacts 4723 in turn make sliding electrical contact with the contacts 4721. From there, further electrical interconnections 4725, 4726 supply power to the plurality of discharge electrodes 4713 and / or the plurality of discharge electrode assemblies 601. The contacts 4721, 4723 may be provided as end face elements (such as flat rings that contact along their flat surfaces), such as as shown in Figure 47B shown. Additionally or alternatively, the contacts 4721, 4723 may be provided as concentric contacts, such as as shown in Figure 47C shown. The contacts may also be used as bearings. In the arrangement of Figure 48 , a centering element 4730 is provided which stabilizes the mounting of the plurality of discharge electrode assemblies 601 on their electrical interconnection 4726 and which itself forms part of the electrical interconnection 4726. The centering element 4730 may be perforated (such as consisting of a plurality of vanes) to allow the gas to flow through it.

[0582] Now referring to Figures 49 to 50 , which schematically shows a plasma delivery tip 4901, 5001 configured with a plurality of longitudinally spaced plasma generation sites 4907 according to some embodiments of the present invention.

[0583] Figure 49 , 50 The arrangement of FIGS. 15 and 16 shows further examples of how to replicate in the design a plasma generation site that by itself provides relatively limited plasma plume coverage and / or move (scan) in operation to expand the coverage area. Design replication allows the design of the plasma delivery tip to be placed as a module of a plurality of independent designs that can be arbitrarily combined on a plurality of individual plasma generation sites. In effect, the modularity "linearizes" a number of other highly non-linear design problems that arise when expanding or otherwise reconfiguring the plasma generation area of a plasma delivery tip design. Thus, for a number of design purposes, the arrangement of the plurality of modules (the plurality of plasma generation sites) can be approximated as simply adding to each other in their respective coverage areas.

[0584] In some embodiments, a plurality of plasma generation sites 4907, 5007 are spaced along a longitudinal axis of the gas supply tubes 119S, 119T; each site includes a module configured to generate its own plasma plume 10Q, 10R. In the example shown, the plurality of plasma generation sites 4907, 5007 are arranged in two rows of alternating plasma generation sites 4907, 5007; the plurality of sites in each row point in radially opposite directions. Optionally, more than two rows of plasma generation sites 4907, 5007 are provided. Optionally, the arrangement of the plurality of plasma generation sites is not a longitudinal arrangement, such as a spiral (e.g., each turn of the spiral having three or more sites). The gas delivery tubes 119S, 119T are rotatable (as shown by the double-headed arrow 5005), separate from or together with the working channel 115 and / or the sleeve 117. In some embodiments, the arrangement of the plurality of plasma generation sites 4907, 5007 is selected such that upon rotation, an effective continuous coverage of a portion of the lumen wall extending along the longitudinal extent of the plasma generation sites is generated.

[0585] The plurality of plasma generation sites 4907 are of the circumferential electrode configuration type, having a discharge electrode 4908 that is at least partially circumferential, which ionizes the ionized gas when the ionized gas flows through a lumen substantially inside the discharge electrode 4908. The plurality of plasma generation sites 5007 are of the type including a discharge electrode assembly 601 that is located within the ionized gas flow - within and / or outside a lumen of the plasma delivery tip (as shown).

[0586] Figures 49 to 50 The plurality of plasma generation sites 4907, 5007 shown are constituted by a plurality of tubes 4910, 5010. As shown, the plurality of tubes are short and annular; they are selected to allow them to be retracted into the lumen space of the sleeve 117 without deformation. Optionally, a plurality of longer tubes are provided, which include a flexible polymer that, for example, folds when confined within the sleeve 117 but expands to point laterally when released from the confinement. Conversely, the plurality of tubes may be omitted, and the plurality of plasma generation sites are simply implemented as a plurality of holes within the gas delivery tubes 119S, 119T, such as those described with respect to Figures 13A to 13B and / or 13D to 13F.

[0587] In the example shown, the plurality of outlet holes of the plurality of plasma generation sites 4907, 5007 are circular; optionally, they have another shape, such as those described with respect to Figures 17A to 19F ...

[0588] In Figure 50In this case, the plurality of discharge electrode assemblies 601 are shown as protruding completely from their respective tubes 5010 to a sufficient distance such that they deflect into a folded state when retracted into the limitations of the sleeve 117 and / or the working channel 115. For example, they can be deflected to the sides and / or mounted on a plurality of elastic members within the lumen 119T, and the plurality of elastic members deflect to allow the plurality of discharge electrode assemblies 601 to be pressed inwardly. Optionally, the plurality of discharge electrode assemblies remain at least partially retracted into their respective tubes 5010; optionally, to such an extent that they do not need to be folded when restricted. The plurality of discharge electrode assemblies 601 can include any one of the plurality of self-actuating (e.g., thermally self-regulating) electrode designs described herein. Also not excluded are a plurality of manually actuated design features, although they can be modified to combine a plurality of components together to form a common actuating member.

[0589] General rules

[0590] As used herein, with respect to a quantity or a value, the term "about" means "within ±10%".

[0591] The terms "comprise, comprising", "include, including", "having" and their plural cognates mean "including but not limited to".

[0592] The term "consisting of" means "including and limited to".

[0593] The term "essentially consisting of" means that the composition, method or structure can include additional components, steps and / or parts, but only if the additional components, steps and / or parts do not substantially change the basic and novel features of the claimed composition, method or structure.

[0594] As used herein, the singular forms "a, an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" can include a plurality of compounds, including mixtures thereof.

[0595] As used herein, the terms "example" and "exemplary" mean "serving as an example, instance, or illustration." Any embodiment described as an "example" or "exemplary" is not necessarily to be construed as preferred or better than other embodiments and / or to exclude the combination of features from other embodiments.

[0596] As used herein, the term "optionally" means "provided in some embodiments but not in other embodiments." Any particular embodiment of the present invention may include a plurality of "optional" features, unless such features are conflicting.

[0597] As used herein, the term "method" refers to a variety of manners, means, techniques, and procedures for accomplishing a particular task, including but not limited to those manners, means, techniques, and procedures that are known or are readily developed by practitioners in the fields of chemistry, pharmacology, biology, biochemistry, and medicine from known manners, means, techniques, and procedures.

[0598] As used herein, the term "treating" includes eliminating, substantially inhibiting, slowing down or reversing the progression of a condition, substantially improving the clinical or aesthetic symptoms of a condition or substantially preventing the appearance of the clinical or aesthetic symptoms of a condition.

[0599] Throughout this application, multiple embodiments may exist in the form of a range. It should be understood that the description in the form of a range is only for convenience and brevity and should not be construed as a rigid limitation on the scope of the present invention. Therefore, it should be considered that the range description has specifically disclosed all possible sub-ranges and the individual values within the range. For example, it should be considered that the range description of "from 1 to 6" has specifically disclosed 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 the range, such as 1, 2, 3, 4, 5, and 6. This applies regardless of the range.

[0600] Whenever a numerical range is indicated herein (e.g., "10-15", "10 to 15", or any pair of numbers indicated by a link to another such range), it means including any number (fractional or integer) within the specified range limits, including the range limits, unless the context clearly dictates otherwise. The phrases "a range between" a first indicated number and a second indicated number and "from" a first indicated number "to", "until", "up to", or "through" (or another such range-indicating term) a second indicated number are interchangeable herein and mean including the first and second indicated numbers, and all fractions and integers therebetween.

[0601] Although the invention has been described in connection with its specific embodiments, it will be apparent that many alternatives, modifications, and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications, and variations that fall within the spirit and scope of the appended claims.

[0602] All publications, patents, and patent applications mentioned in this specification are hereby incorporated by reference in their entirety into this specification. To the extent that each individual publication, patent, or patent application is specifically and individually indicated as being incorporated by reference herein. Additionally, any reference cited or pointed out should not be construed as an admission that such reference is available as prior art to the present invention. The title portion of this application is used herein to make the specification readily understandable and should not be construed as a necessary limitation. Additionally, any priority documents of this application are hereby incorporated by reference in their entirety into this application.

[0603] It will be understood that the specific features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features described in the context of a single embodiment for brevity may also be provided separately, or in any suitable sub-combination, or in any other described embodiment applicable to the invention. The specific features described in the context of the various embodiments are not to be considered essential features of those embodiments unless the embodiment cannot function without those elements.

Claims

1. A plasma delivery tip of a medical-grade plasma generation device, characterized in that: the plasma delivery tip comprises: a gas delivery lumen having a proximal-to-distal axis, and an ionized gas flow flowing axially distally towards an exit orifice of the gas delivery lumen; and a discharge electrode located within the lumen for generating plasma within the lumen, electrically isolated from the ionized gas flow by a dielectric barrier layer, and when attached to a high-voltage power source, transmitting a high-voltage gradient into the ionized gas flow, the gradient acting to generate a plurality of free electrons beside the discharge electrode and generating a cold plasma flow by dielectric barrier discharge; wherein the exit orifice of the gas delivery lumen is oriented to direct a cold plasma plume to exit the gas delivery lumen along an inclined direction oriented away from the proximal-to-distal axis, wherein the plasma delivery tip is adapted for intracavitary delivery using a sheath or working channel and has an outer diameter of less than 7 mm; and wherein the discharge electrode comprises a core center conductor of a coaxial cable, the coaxial cable comprising the core center conductor and an outer conductor, and the core center conductor extends distally beyond the outer conductor and transmits the high-voltage gradient.

2. The plasma delivery tip according to claim 1, characterized in that: the gas delivery lumen comprises a plurality of exit orifices, the plurality of exit orifices being oriented along an inclined direction away from the axis including the exit orifice, and wherein the discharge electrode extends circumferentially around the gas delivery lumen.

3. The plasma delivery tip according to claim 1, characterized in that: the plasma delivery tip comprises: at least one gas return channel extending along the gas delivery lumen, the ionized gas flow returning proximally through the gas return channel after exiting the gas delivery lumen.

4. The plasma delivery tip according to claim 3, characterized in that: the at least one gas return channel extends helically around the gas delivery lumen.

5. The plasma delivery tip according to claim 3 or 4, characterized in that: the gas return channel is provided with a connector to allow attachment to a negative pressure source.

6. The plasma delivery tip according to claim 3 or 4, characterized in that: the gas return channel is open to a pressure below that which generates negative pressure.

7. The plasma delivery tip according to claim 3 or 4, characterized in that: the plasma is thermally non-damaging.

8. The plasma delivery tip according to claim 1, characterized in that: the plasma delivery tip comprises: an outer insulating layer of the coaxial cable, which surrounds the outer conductor of the coaxial cable and is stripped from a distal portion of the core center conductor; wherein the outer conductor comprises a flexible conductive electromagnetic shielding layer extending distally from a distal portion of the coaxial cable, the coaxial cable comprising a reinforced electromagnetic shielding layer; and an insulator that insulates the core center conductor with a dielectric barrier layer, the dielectric barrier layer extending distally beyond the outer conductor.

9. The plasma delivery tip according to claim 8, characterized in that: The plasma delivery tip includes adding an outer insulating layer to extend over the enhanced electrical shielding layer.

10. The plasma delivery tip according to claim 8 or 9, wherein: the coaxial cable has an outer diameter less than 4 mm.

11. The plasma delivery tip according to any one of claims 1 to 4, wherein: the plasma delivery tip is provided with the plasma generating device and is operable to generate plasma.

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