Plasma processing apparatus and method of using the same

Abstract

A medical device for generating aerosols and plasmas, such as for therapeutic treatments, is described. The medical device may include a nebulizer including an outer compartment, an inner compartment, and a needle radially inward of the inner and outer compartments. The medical device may include at least one electrode and a chamber, the distal-facing surface of the chamber defining at least one plasma outlet, a nozzle in communication with the nebulizer, and an end of the electrode proximal to the plasma outlet.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority to U.S. Provisional Patent Application No. 62 / 828,797, filed on April 3, 2019, the contents of which are incorporated herein by reference in their entirety.

[0002] This disclosure generally relates to plasma processing apparatuses and methods of using the same.

Background Art

[0003] Plasma devices are used in medical surgery and sterilization methods. In industrial applications other than medical, plasma devices are used to create thin - film coatings such as polymer coatings. The method of depositing polymers with a plasma device often depends on the presence of precursors that are reactive in the plasma to form a polymer coating during the deposition process. Such conditions can induce polymerization and can damage various species present in the plasma.

Summary of the Invention

Means for Solving the Problems

[0004] This disclosure includes a medical device for generating an aerosol and a plasma for therapeutic treatment and the like. For example, the medical device is a housing comprising a nebulizer, the nebulizer having an external compartment in communication with a gas inlet, an internal compartment in communication with a fluid channel, a fluid inlet, and a needle, the needle being radially inward of the internal compartment, the internal compartment being radially inward of the external compartment, the distal end of the external compartment being in communication with the distal end of the internal compartment, the housing, at least one electrode, and a chamber defined by a distal end portion of the housing, the distal opposing surface of the chamber defining at least one plasma outflow portion and a nozzle in communication with the nebulizer, the end of the electrode being at the plasma outflow portion proximate to , a chamber, and may comprise.

[0005] In the embodiments of this specification, the proximal portion of the chamber may be configured to receive the electrode tip of the plasma device and electrically connect the electrode tip of the plasma device to the electrode of the plasma outflow portion, and / or the distal portion of the housing may include an actuator configured to control the flow rate of the gas into the gas inlet. The longitudinal position of the needle of the nebulizer may be adjustable.

[0006] According to some embodiments of the present disclosure, the medical device may further include a plasma device, wherein the actuator of the housing can be arranged relative to the actuator of the plasma device such that the user controls the gas flow rate and simultaneously outputs a supply to the plasma device. In other embodiments, the medical device may further include a fluid reservoir connected to the fluid inlet. The fluid reservoir may include a fitting element complementary to the fitting element of the fluid inlet such that the fluid reservoir can be selectively separated from the fluid inlet. In at least one embodiment, the fluid reservoir contains a liquid containing at least one therapeutic agent.

[0007] According to some aspects of the present disclosure, the at least one therapeutic agent includes a biomolecule, a pharmaceutical agent, or a combination thereof. In some embodiments, the at least one therapeutic agent is dissolved in a solvent.

[0008] In some embodiments of this specification, the housing defines a first channel communicating with the outer compartment of the nebulizer, a second channel including an electrode, and a distal end of the second channel that defines the plasma outflow portion. In at least one embodiment, at least one electrode extends through the wall of the chamber.

[0009] The present disclosure also relates to a housing comprising a nebulizer, wherein the nebulizer comprises an outer compartment, an inner compartment, and a needle, the needle being radially inward of the inner compartment, the inner compartment being radially inward of the outer compartment, the distal end of the outer compartment communicating with the distal end of the inner compartment, and a fluid reservoir connected to the fluid inlet and containing a liquid comprising at least one therapeutic agent, at least one electrode, and a chamber defined by a distal end portion of the housing, the distal facing surface of the chamber defining at least one plasma outflow portion and a nozzle communicating with the nebulizer, and the end of the electrode being at the plasma outflow portion proximate to and a chamber. The disclosure includes a medical device.

[0010] In some embodiments of the present disclosure, the fluid reservoir may comprise a fitting element complementary to the fitting element of the fluid inlet such that the fluid reservoir is selectively separable from the fluid inlet. In at least one example, the fluid reservoir is permanently installed at the fluid inlet. In some examples, the outer compartment of the nebulizer communicates with a gas inlet, and the inner compartment of the nebulizer communicates with the fluid inlet. In at least one example, the end of the electrode is a recess on the distal facing surface of the chamber. According to some aspects of the present disclosure, the housing defines a first channel communicating with the outer compartment of the nebulizer, a second channel containing the electrode, and the distal end of the second channel defining the plasma outflow portion. In at least one example, the at least one therapeutic agent includes a biomolecule, a pharmaceutical agent, or a combination thereof.

[0011] The present disclosure also relates to a housing comprising a nebulizer, the nebulizer comprising an external compartment in communication with a gas inlet, an internal compartment in communication with a fluid channel, and a needle, the needle being radially inward of each of the internal and external compartments, the distal end of the external compartment communicating with the distal end of the internal compartment, the housing further comprising at least one electrode, a fluid reservoir connected to the fluid inlet, and a chamber defined by a distal end portion of the housing, the distal facing surface of the chamber defining at least one plasma outlet and a nozzle in communication with the nebulizer, the end of the electrode being at the plasma outlet proximate to and the chamber, and includes a medical device.

[0012] The present disclosure also includes a method of treating tissue of a subject. For example, the method can include exposing the tissue to a plasma and / or aerosol comprising at least one therapeutic agent using any of the medical devices described herein. The tissue can be internal or external tissue. In some embodiments, the tissue can be part of a wound, burn, incision, ulcer, abrasion, or tumor. In at least one embodiment, the subject is a human subject. In some embodiments, the method includes generating the plasma at a frequency in the range of about 150 kHz to about 500 kHz.

[0013] According to some aspects of the present disclosure, the at least one therapeutic agent includes a biomolecule, a pharmaceutical agent, or a combination thereof. In some embodiments, the at least one therapeutic agent includes collagen.

[0014] The method can further include supplying fluid to the nebulizer and simultaneously supplying an output to at least one electrode such that the aerosol exits the nozzle simultaneously with the plasma exiting the plasma outlet. Supplying the fluid and supplying the output can include pressing a single actuator of the medical device. In at least one embodiment, pressing the single actuator and supplying the output can include pressing a single actuator of the medical device The present invention provides, for example, the following. (Item 1) A medical device comprising: A housing having a nebulizer, the nebulizer comprising: An outer compartment in communication with a gas inlet; A fluid channel and an inner compartment in communication with a fluid inlet; A needle, wherein the needle is radially inside the inner compartment, the inner compartment is radially inside the outer compartment, and a distal end of the outer compartment communicates with a distal end of the inner compartment, and the housing comprising the needle; At least one electrode; A chamber defined by a distal end portion of the housing, wherein a distal facing surface of the chamber defines at least one plasma outflow portion and a nozzle in communication with the nebulizer; wherein an end of the electrode is at the plasma outflow portion proximate to and the chamber, and the medical device. (Item 2) The medical device according to item 1, wherein a proximal portion of the chamber receives an electrode tip of a plasma device and is configured to electrically connect the electrode tip of the plasma device to the electrode at the plasma outflow portion. (Item 3) The medical device according to item 1, wherein a longitudinal position of the needle of the nebulizer is adjustable. (Item 4) The medical device according to item 1, wherein a distal portion of the housing comprises an actuator configured to control a flow rate of gas to the gas inlet. (Item 5) The medical device according to item 4, further comprising a plasma device, wherein the actuator of the housing is arranged relative to an actuator of the plasma device such that the user controls a flow rate of gas and simultaneously outputs a supply to the plasma device. (Item 6) The medical device according to item 1, further comprising a fluid reservoir connected to the fluid inlet. (Item 7) The medical device according to item 6, wherein the fluid reservoir comprises a fitting element complementary to the fitting element of the fluid inlet so that the fluid reservoir is selectively separable from the fluid inlet. (Item 8) The medical device according to item 6, wherein the fluid reservoir contains a liquid containing at least one therapeutic agent. (Item 9) The medical device according to item 8, wherein the at least one therapeutic agent comprises a biomolecule, a pharmaceutical agent, or a combination thereof. (Item 10) The medical device according to item 8, wherein the at least one therapeutic agent is dissolved in a solvent. (Item 11) The medical device according to item 1, wherein the housing comprises a first channel communicating with the external compartment of the nebulizer, a second channel containing the electrode, and defines a distal end of the second channel that defines the plasma outflow portion. (Item 12) The medical device according to item 1, wherein the at least one electrode extends through the wall of the chamber. (Item 13) A medical device, A housing comprising a nebulizer, wherein the nebulizer comprises An external compartment, and An internal compartment, and A needle, wherein The needle is radially inside the internal compartment, the internal compartment is radially inside the external compartment, and the distal end of the external compartment communicates with the distal end of the internal compartment, and a housing comprising the needle, A fluid reservoir connected to a fluid inlet and containing a liquid containing at least one therapeutic agent, At least one electrode, and A chamber defined by a distal end portion of the housing, wherein The distal facing surface of the chamber defines at least one plasma outflow portion and a nozzle communicating with the nebulizer, The end of the electrode is the plasma outflow part proximate to , a chamber, and a medical device. (Item 14) The fluid reservoir of the medical device according to item 13, wherein the fluid reservoir has a fitting element complementary to the fitting element of the fluid inlet so that the fluid reservoir can be selectively separated from the fluid inlet. (Item 15) The fluid reservoir of the medical device according to item 13, which is permanently installed in the fluid inlet. (Item 16) The external compartment of the nebulizer communicates with the gas inlet, and the internal compartment of the nebulizer communicates with the fluid inlet. The medical device according to item 13. (Item 17) The end of the electrode is a recess on the distal facing surface of the chamber. The medical device according to item 13. (Item 18) The housing has a first channel communicating with the external compartment of the nebulizer, a second channel including the electrode, and a distal end of the second channel defining the plasma outflow part. The medical device according to item 13. (Item 19) The at least one therapeutic agent includes a biomolecule, a pharmaceutical agent, or a combination thereof. The medical device according to item 13. (Item 20) A medical device, A housing having a nebulizer, the nebulizer An external compartment communicating with a gas inlet, An internal compartment communicating with a fluid inlet, A needle, The needle is radially inside each of the internal compartment and the external compartment, and the distal end of the external compartment communicates with the distal end of the internal compartment. A housing having a needle, At least one electrode, A fluid reservoir connected to the fluid inlet, A chamber defined by a distal end portion of the housing, The distal facing surface of the chamber defines at least one plasma outflow portion and a nozzle in communication with the nebulizer, The end of the electrode is the plasma outflow portion proximate to , a chamber, and a medical device. (Item 21) A method of treating a target tissue, the method comprising exposing the tissue to a plasma and / or aerosol containing at least one therapeutic agent using the medical device according to any one of Items 1 to 21. (Item 22) The method according to Item 21, wherein the tissue is an internal tissue or an external tissue. (Item 23) The method according to Item 21, wherein the tissue is a wound, a burn, an incision, an ulcer, an abrasion, or a tumor part. (Item 24) The method according to Item 21, wherein the subject is a human subject. (Item 25) The method according to Item 21, wherein the method includes generating the plasma at a frequency in the range of about 150 kHz to about 500 kHz. (Item 26) The method according to Item 21, wherein the at least one therapeutic agent includes a biomolecule, a pharmaceutical agent, or a combination thereof. (Item 27) The method according to Item 21, wherein the at least one therapeutic agent includes collagen. (Item 28) The method according to Item 21, wherein the method includes supplying a fluid to the nebulizer and simultaneously supplying an output to the at least one electrode such that the aerosol exits the nozzle simultaneously with the plasma exiting the plasma outflow portion. (Item 29) The method according to Item 28, wherein supplying the fluid and supplying the output includes pressing a single actuator of the medical device. (Item 30) The method of claim 29, wherein pressing the single actuator actuates the output button of the medical device aligned with the single actuator. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate specific features of the disclosure and, together with the description, serve to explain the principles of the disclosure. Those skilled in the art will readily appreciate that the features of a particular aspect or embodiment can be used in combination with any or all of the features of other aspects or embodiments described in this disclosure.

[0016]

Figure 1

Figure 2

Figure 3A

Figure 3B

Figure 4

Figure 5A

Figure 5B

Figure 5C

Figure 5D

Figure 5E

Figure 6A

Figure 6B

Figure 6C

Figure 7A

Figure 7B

Mode for Carrying Out the Invention

[0017] The present disclosure generally includes systems, devices, and methods for delivering an active therapeutic agent (e.g., a biomolecule, a pharmaceutically active agent, and / or a combination thereof) together with plasma to a surface (e.g., a tissue surface or a non-tissue substrate).

[0018] The singular articles "a", "an", and "the" include things that indicate a plurality unless otherwise specified in the context. The term "about" indicates being almost the same as the reference number or value. The term "about" as used herein should generally be understood to encompass ±5% of a particular quantity or value. All ranges are understood to include endpoints, for example, a distance between 1.0 cm and 5.0 cm includes the distances of 1.0 cm, 5.0 cm, and all values therebetween.

[0019] The systems and devices herein can be used to apply a therapeutic agent to the external and / or internal tissues of a subject such as a human or a non-human animal. For example, the therapeutic agent and / or plasma can contribute to healing. The systems and devices herein can be configured to deliver one or more therapeutic agents within and / or adjacent to the plasma, and can be configured to deliver the therapeutic agent before, during, and / or after treating the tissue with the plasma. The therapeutic agent can further be delivered, for example, by proximate and / or a mixed aerosol mixed with the plasma. In some embodiments, the therapeutic agent includes one or more pharmaceutical agents and / or biomolecules that do not contain vinyl groups or other chemical functional groups where polymerization is assumed under non-thermal equilibrium plasma conditions. The systems and devices herein can be used to treat various medical conditions including, but not limited to, internal and / or external burns, wounds, cuts, incisions, ulcers, abrasions, and tumors.

[0020] The plasma can be non-thermal equilibrium or cold plasma, such as to minimize damage to the therapeutic agent, tissue damage, and / or discomfort to the subject. For example, the plasma may be output-supplied at a frequency in the range of about 150 kHz to about 500 kHz, such as about 200 kHz to about 450 kHz, or about 150 kHz to about 300 kHz. In some embodiments herein, the maximum frequency can be less than 900 kHz, such as less than 700 kHz, less than 600 kHz for example. In at least one aspect, the plasma is pulsed plasma. The plasma can be pulsed oscillated at various duty cycles such that the supply output is less than 100 W, such as less than 20 W or less than 10 W. The applied output may be pulsed oscillated such that the pulse is off for at least 50% of that time, such as the pulse is switched on and off a large number of times per second for example. For example, the plasma can be pulsed oscillated on and off to supply an on-time in the range of about 1 ns to about 500 ms. For example, the plasma may be pulsed oscillated with an on-time in the range of 1 ms to 500 ms, such as 10 ms to 300 ms, 50 ms to 100 ms, etc., such as about 1 ms, about 10 ms, about 50 ms, about 75 ms, about 100 ms, about 200 ms, about 250 ms, about 300 ms, about 400 ms, or about 500 ms etc. For example, for the treatment of tissue, the plasma can be nanosecond or picosecond pulsed plasma. In these examples, the plasma may be on only during the time divided in milliseconds for each pulse, such as less than 500 ns or less than 100 ns for each pulse.

[0021] While a typical apparatus is described herein and illustrated by specific configurations and components, it will be apparent to those skilled in the art that variations of the apparatus are also included herein. For example, the components of the illustrated apparatus can be arranged in a different configuration or can be completely omitted. Further, additional components may be added to the apparatus in view of the description herein and in accordance with the disclosed principles.

[0022] Figures 1 to 3B show the features of a typical device 100 that can be used to deliver one or more therapeutic agents in conjunction with plasma. For example, FIG. 1 shows a device 100 comprising an adapter 120 coupled to a plasma device 180 for generating non-thermal plasma. The plasma device 180 comprises a body with an output button 185, and a distal end portion 184 including a distal tip 182. The distal tip 182 may comprise an electrode coupled to a power source and a gas source controlled by the output button 185. Thus, when the output button 185 of the plasma device 180 is actuated, simultaneous delivery of gas and alternating current to the distal tip 182 is initiated to generate plasma. The adapter 120 may be configured to couple to the distal end portion 184 of the plasma device 180 in a separable manner or the like. The adapter may enable simultaneous and / or continuous deposition of an aerosol containing one or more therapeutic agents by the plasma generated by the plasma device 180.

[0023] As shown in FIG. 1, the adapter 120 comprises a proximal opening 102 for receiving the distal end portion 184 of the plasma device 180. The adapter 120 may be fixed to the plasma device 180 by any suitable coupler or mechanism, such as a friction fit (e.g., the inner surface of the proximal opening 102 containing an elastomeric material), a clip, a screw, a thread, etc. The adapter 120 further comprises a distal end portion 104 defining an outflow chamber 116, a nebulizer 106, a gas inlet 108, and a fluid reservoir 110. The gas inlet 108 may be coupled to a gas source such as a medical gas system or a portable cylinder of compressed gas. Exemplary gases that may be used in the devices and systems herein include, but are not limited to, air (including medical air), nitrogen, helium, argon, and mixtures thereof. The gas inlet 108 and the fluid reservoir 110 communicate with the nebulizer 106. The fluid reservoir 110 may be integral or permanent to the adapter 120, or the fluid reservoir 110 may be coupled to the adapter 120 by a suitable coupler such as a luer fitting. In some embodiments herein, the fluid reservoir 110 may be in the form of a syringe. FIGS. 5A - 5E show additional embodiments of fluid reservoirs that may be used in the device 100 and / or any other device herein.

[0024] The gas can be adjusted by fixing or varying the pressure and / or flow rate. For example, the gas can be adjusted at a pressure of about 30 psi to about 40 psi, such as about 35 psi. In some embodiments of the present disclosure, the flow rate of the gas used to generate the plasma can be in the range of about 1 liter per minute (L / min) to about 10 L / min, such as about 1 L / min to about 5 L / min, about 5 L / min to about 7 L / min, or about 4 L / min to about 6 L / min.

[0025] The adapter 120 further comprises an actuator 112 configured to control the flow rate of the gas to the nebulizer 106 by means of a valve (which can be mechanical or electrical). Thus, for example, the user can control the flow rate of the gas to the adapter 120 by means of the actuator 112 and then control the generation of the aerosol by means of the nebulizer 106. That is, when gas begins to flow into the gas inlet 108, the pressure of the nebulizer 106 changes. The fluid contained within the fluid reservoir 110 can communicate with the nebulizer 106 such that the fluid is drawn from the fluid reservoir 110 to the nebulizer 106 due to the pressure change. Thus, for example, the fluid can be drawn to the nebulizer 106 in the absence of an external force or a system that pushes the fluid, such as an external pump, a liquid delivery system, or external pressurization, to the nebulizer 106. That is, the pressure change can be sufficient to draw the fluid from the fluid reservoir 110. Thereafter, the gas and the fluid exit the nebulizer 106 via the nozzle 142 at the distal end portion 104 of the adapter 120. Further details of the nebulizer 106 are shown in FIG. 2.

[0026] Referring further to FIG. 1, when the adapter 120 is coupled to the plasma device 180, the actuator 112 can be arranged such that the actuator 112 is installed above the output button 185, allowing the user to simultaneously generate aerosol and plasma. Thus, for example, once the plasma device 180 is mated to the adapter 120 (e.g., the distal end portion 184 of the plasma device 180 is inserted into the proximal opening 102 of the adapter 120), pressing the actuator 112 downward opens the valve to supply gas and further activates the output button 185 of the plasma device 180. The plasma generated by the plasma device 180 can enter the chamber 116 via one or more plasma outflow portions 140.

[0027] According to some embodiments of the present specification, the actuator 112 can be configured to allow the user to separately and independently control the aerosol and the plasma. For example, the actuator 112 can include a first portion that actuates a valve to supply gas and a second portion that actuates the output button 185, and the first and second portions can be pressed separately, continuously, or simultaneously.

[0028] The fluid reservoir 110 can be open or closed, such as being placed with a plunger or a cap so that the fluid does not overflow from the fluid reservoir 110. In some embodiments, the fluid reservoir 110 may include a vented plunger or cap, for example, to equalize the pressure when the liquid exits. The fluid reservoir 110 can be coupled to the nebulizer 106 at an appropriate angle to allow the fluid contained within the fluid reservoir 110 to flow by gravity into a channel communicating with the nebulizer 106. According to some aspects of the present disclosure, the fluid reservoir 110 may be positioned at an angle of less than 90 degrees with respect to the longitudinal axis of the nebulizer 106. For example, the fluid reservoir 110 can be positioned at an angle in the range of about 10 degrees to about 85 degrees or about 30 degrees to about 60 degrees, such as an angle of about 80 degrees, about 70 degrees, about 60 degrees, about 50 degrees, or about 40 degrees.

[0029] The fluid contained within the fluid reservoir 110 is compatible with the therapeutic agent and can include any suitable liquid that is suitable for generating an aerosol. The liquid may contain, consist of, or consist essentially of one or more therapeutic agents. The therapeutic agent can be dissolved or otherwise mixed with a solvent such as water or other aqueous solution, or an alcohol or other organic solvent. Typical solvents include, but are not limited to, acetic acid and acetic acid solutions, ethanol and ethanol solutions, water containing acidified water (e.g., pH greater than 3 but less than 7), physiological saline, solutions containing free amino acids, sulfate solutions, polyelectrolytes such as polyphosphates or sulfated polysaccharides, complexing agents, and mixtures thereof. In some embodiments, the solvent can include alcohols such as methanol, ethanol, propanol, butanol, polyvinyl alcohol, benzoyl alcohol, fatty alcohols, lanolin alcohol, glycerol, ethylene glycol, polyethylene glycol, and mixtures thereof, organic solvents such as dimethyl sulfoxide (DMSO), isopropyl myristate, oleic acid, acetone, chloroform, ethyl acetate, azone (laurocapram), urea, essential oils, fatty acids, oxazolidinone, terpenes, terpenoids, and mixtures thereof. Further typical organic solvents include organic compounds such as pyrrolidones such as polyvinylpyrrolidone (PVP), cyclodextrins, etc., dissolved in a suitable liquid such as water or an organic liquid.

[0030] Typical therapeutic agents that can be delivered with the devices of this specification include, but are not limited to, pharmaceutical agents, biomolecules, and mixtures thereof. In some embodiments, the liquid can include one or more pharmaceutically active materials, biomolecules, antibiotics, penetration enhancers, carriers, preservatives, proteins, biopolymers, synthetic biodegradable polymers, or combinations thereof. Typical therapeutic agents include collagen, fibrin, elastin, fibronectin, hyaluronic acid, chitosan, alginate, cellulose, phosphorylcholine, polypeptides, polyglycans, hormones, lipids, interferons, cartilage, recombinant blood cells, synthetically derived blood cells, platelet-rich plasma, cells (autologous or donor cells), melanocytes, stem cells, antibacterial agents, antibiotics, bacteriostatic agents, antibodies (including monoclonal antibodies), stem cells, amniotic materials, bovine serum albumin, proteins, clotting factors, growth factors, cytokines, chemotherapeutic agents, anti-inflammatory agents, immunosuppressive agents, analgesics, blood pressure medications, antithrombotic agents, anticoagulants, antiplatelet agents, thrombolytic agents, antiproliferative agents, antimitotic agents, agents that inhibit restenosis, smooth muscle cell inhibitors, fibrinolytic agents, immunosuppressive agents, angiogenesis inhibitors, vaccines, and combinations thereof, but are not limited thereto. For example, the liquid can include collagen, plasma, chitosan, or combinations thereof.

[0031] Referring to FIGS. 1 and 2, nebulizer 106 can be a nebulizer including any suitable atomizer or nebulizer such as ultrasonic, piezoelectric, pneumatic, mechanical, electric, vibrating mesh, or jet nebulizers. Nebulizer 106 can include an outer compartment 106a, an inner compartment 106b, a needle 107, and a threaded coupler 107a. The outer compartment 106a and the inner compartment 106b can be concentric with each other and arranged such that the distal outflow of the outer compartment 106a communicates with the distal outflow of the inner compartment 106b. The needle 107 can be radially inward of both the outer compartment 106a and the inner compartment 106b, such as being contained within the inner compartment 106b.

[0032] According to some aspects of the present disclosure, the fluid reservoir 110 can be disposed relatively close to the nebulizer. For example, the fluid reservoir 110 can be disposed less than about 50 mm from the nebulizer 106, such as from about 1 mm to about 50 mm. For example, the fluid reservoir 110 can be disposed less than about 45 mm, less than about 40 mm, less than about 35 mm, less than about 30 mm, or less than about 25 mm from the nebulizer 106. Without being bound by theory, it is believed that disposing the fluid reservoir 110 relatively close to the nebulizer 106 can efficiently transport the fluid. For example, the fluid may be supplied to the nebulizer in the absence of an injector pump or piping or other liquid lines.

[0033] The outer compartment 106a can communicate with a gas source, and the inner compartment 106b can communicate with a fluid source. For example, as shown in FIG. 2, the gas inlet 108 connects the gas source to the outer compartment 106a of the adapter 120 such that gas passes through the gas inlet 108 and is supplied to the outer compartment 106a of the nebulizer 106. Similarly, the fluid inlet 109 connects a fluid source (e.g., fluid reservoir 110) to the inner compartment 106b. As described above, the fluid contained within the fluid reservoir 110 can enter a fluid channel that communicates with the inner compartment 106b of the nebulizer 106. Thus, for example, when the gas flow is on, the pressure change within the adapter 120 may cause the fluid to be drawn from the fluid reservoir 110 into the inner compartment 106b. Thereafter, the gas and fluid exit as an aerosol through the distal outflow portions of the outer compartment 106a and the inner compartment 106b, respectively, via the nozzle 142 at the distal end portion 104 of the adapter 120. When the aerosol exits the nozzle 142, it is introduced into the outflow chamber 116 via the plasma outflow 140 adjacent the nozzle 142 so that the aerosol can mix with the plasma entering the chamber 116 before the aerosol contacts the surface to be treated with the plasma and the therapeutic agent. The outflow chamber 116 can have dimensions defining a volume sufficient to mix the aerosol with the plasma prior to deposition on the surface of the tissue to be treated or the like. The outflow chamber 116 can have various shapes, for example, a conical shape in which the distal end of the outflow chamber 116 can flare out such that the cross-sectional dimension at the distal end of the chamber 116 is larger than the cross-sectional dimension at the proximal end of the chamber 116. The flared conical shape can enable the plasma and the aerosol to impinge on a relatively large surface area to be treated and sprayed. In some embodiments, the chamber 116 can be narrow at the distal end, for example, to direct or concentrate the flow of the aerosol and the plasma more precisely onto the surface to be treated. According to some aspects of the present disclosure, the length of the chamber is in the range of about 10 mm to about 100 mm, such as about 30 mm to about 50 mm, or about 35 mm to about 45 mm. Further, for example, the chamber can have a cross-sectional shape with an inner diameter in the range of about 6 mm to about 50 mm, such as about 10 mm to about 30 mm, or about 15 mm to about 25 mm.

[0034] In embodiments of the present disclosure, the outer compartment 106a and the inner compartment 106b may be tapered towards the nozzle 142 by or it proximate to towards the needle 107. In some embodiments, the tip of the needle 107 may be coplanar with the proximal wall of the outflow chamber 116, or the tip may project into the outflow chamber 116. In either case, the tip of the needle 107 can be positioned relative to the nozzle 142 such that the aerosol enters the chamber 116.

[0035] Without being bound by theory, it is believed that the radial cross-section of the outer and inner compartments 106a, 106b decreases, accelerating the gas and liquid flow, thereby reducing the pressure. This pressure change provides a Venturi effect to the inner compartment 106b, and the pressure is lower at the distal outflow of the inner compartment 106b relative to the pressure in the fluid reservoir 110. When the outer compartment 106a is pressurized, the fluid contained in the reservoir 110 is drawn into the inner compartment 106b of the nebulizer 106. When the liquid exits the inner compartment 106b above the tip of the needle 107, it can be atomized by the gas exiting the outer compartment 106a through the nozzle 142 to create an aerosol in the outflow chamber 116.

[0036] In some embodiments of the present disclosure, the distal end of the outer compartment 106a communicates with the distal end of the inner compartment 106b via an opening having an annular shape. For example, the opening may have a uniform annular shape, such that a uniform flow of gas exits the outer compartment 106a, contacts the liquid from the inner compartment 106b, and then exits through the nozzle 142 into the outflow chamber 116. Adjusting the shape and / or size of the opening, such as by adjusting the position of the needle 107, can change the gas flow rate and, as a result, the shape and / or volume of the resulting spray. For example, a flat orifice may produce a fan-shaped spray. In embodiments of the present disclosure, the spray of the atomized fluid has a uniform conical shape. Further, reducing the annular distance between the inner diameter of the outer compartment 106a and the outer diameter of the inner compartment 106b can increase the velocity of the gas exiting the distal end of the outer compartment 106a. An increase in the gas flow velocity is expected to further reduce the pressure at the distal end of the inner compartment 106b.

[0037] According to some aspects of the present disclosure, a uniform annular opening is provided between the inner compartment 106b and the tip of the needle 107. The size of the annular opening can limit the amount of fluid exiting the distal end of the inner compartment 106b. Without being bound by theory, the orientation of the distal end of the needle 107, the distal ends of the inner compartment 106b and the outer compartment 106a, respectively, can characterize the performance of the nozzle 142 when generating an aerosol. The outer compartment 106a may have a nozzle throat corresponding to the minimum diameter portion of the distal end of the outer compartment 106a. The dimensions of the throat relative to the remainder of the nozzle 142 and the pressure of the inflowing gas can determine the pressure within the nozzle 142 and, thus, the strength of the Venturi effect. The distal end of the inner compartment 106b is positioned such that the pressure at the nozzle throat is lower than the pressure within the fluid reservoir 110 at the portion of the nozzle throat of the outer compartment 106a to or that proximate to itor can be outside the nozzle throat of the outer compartment 106a. Otherwise, the pressure within the nozzle can be above atmospheric pressure, and the fluid can be prevented from flowing from the fluid reservoir 110 into the inner compartment 106b. Instead, gas may flow into the fluid reservoir 110. The distal end of the inner compartment 106b can also be in close proximity to the distal end of the outer compartment 106a such that the gas flow can atomize the liquid. If the distal end of the inner compartment 106b is too far from the distal end of the outer compartment 106a, the liquid may form relatively large droplets.

[0038] The threaded connector 107a of the nebulizer 106 can be attached to or integral with the proximal end of the needle 107, and the threaded connector 107a can engage a female thread at the proximal portion of the inner compartment 106b. The needle 107 can be retracted or advanced by rotating the threaded connector 107a, thereby increasing or decreasing the aerosol flow from the nozzle 142. The threaded connector 107a can be fixed or adjustable. In an embodiment of the present disclosure, the needle 107 is advanced and can be positioned against the inner surface of the distal end of the inner compartment 106b. Further advancing the needle 107 can result in positioning the distal end within the distal end of the outer compartment 106a, and thereby slightly deforming the distal end of the inner compartment 106b. Retracting the needle 107 sets an annular space between the needle 107 and the distal end of the inner compartment 106b and regulates the generation of aerosol passing through the fluid path and the nozzle 142.

[0039] The needle 107 can include any suitable material or combination of materials. Exemplary materials useful for the needle 107 include, but are not limited to, metals and metal alloys such as stainless steel. When the fluid exits the distal end of the internal compartment 106b above the surface of the needle 107, it is atomized by the gas flow from the distal end of the external compartment 106a. If the needle 107 is too long (e.g., the needle 107 protrudes into the chamber 116), some or all of the fluid may flow along the surface of the needle 107 and leave the distal end of the needle 107 as relatively large droplets. The shape of the aerosol spray exiting the nozzle 142 may also be affected by the shape of the needle 107 and / or the position of the needle 107 relative to the distal ends of the respective external compartment 106a and internal compartment 106b. The shape of the nebulizer 106 and / or the nozzle 142 can be configured to provide a desired spray radius and the angle formed by the spray. For example, an obtuse angle means a relatively wide spray radius, while an acute angle means a relatively small spray radius. In some embodiments, the distance between the tip of the needle 107 and the distal end of the internal compartment 106b can range from about 15 mm to about 25 mm, or from about 5 mm to about 60 mm such as about 15 mm to about 25 mm.

[0040] The surface of the needle 107 can be sufficiently smooth such that the fluid flows uniformly over the surface and the fluid is atomized uniformly. For example, the surface of the needle can be smoothed by polishing or a similar process. In some embodiments, the needle 107 may have a surface polished with an 800 grit abrasive.

[0041] Figures 3A and 3B respectively show perspective views of the distal and proximal ends of the outflow chamber 116. As shown, the proximal side of the outflow chamber 116 may include a hypo tube 132, at least two electrodes 130, and a housing 136 that extends in the proximal direction surrounding the nebulizer 106. The hypo tube 132 may be a tubular structure configured to receive the distal tip 182 of the plasma device 180 and may optionally have an angled tip. In some embodiments, the hypo tube 132 is connected to the chamber 116 by an adhesive such as a photo-curable adhesive. The hypo tube 132 may include any suitable material such as a metal or metal alloy.

[0042] The hypo tube 132 may communicate with the electrodes 130 by means of conducting wires or the like. The electrodes 130 may be separately housed, for example, in a pipe that can be connected to the proximal side of the outflow chamber 116 by a suitable mounting structure. In some embodiments, the adapter 120 may include only one electrode 130 or three or more electrodes 130. For example, the adapter 120 may include three or more electrodes 130 arranged within a ring. As described above, the hypo tube 132 may be connected to each of the electrodes 130 by a conductor material such as a copper wire surrounded by an insulating material such as a polymer coating. The insulated wire may be connected to the hypo tube 132 and fixed in place by an insulating material such as a silicon pipe sleeve. The silicon pipe sleeve and the photo-curable adhesive may electrically insulate the hypo tube 132 and the electrodes 130, minimizing the electrical energy loss at the joints of the respective electrodes 130. The electrodes 130 may be housed within a suitable insulating material such as plastic or silicon.

[0043] In some embodiments of the present disclosure, electrode 130 may include pins that can be coplanar with the wall of the outflow chamber 116 and can be recessed or protruded into the outflow chamber 116. In at least one embodiment, the pins of electrode 130 are recessed or protruded into chamber 116 by a distance of about 0.1 mm to about 3 mm, such as about 1 mm to about 2.5 mm, or about 1.5 mm to about 2.0 mm. Without being bound by theory, it is believed that having the pins of electrode 130 recessed into chamber 116 may increase the intensity of the plasma discharge.

[0044] In some embodiments, hypo-tube 132 may pass through outflow chamber 116 and may have an inner cross-sectional area that is substantially the same as the annular outer cross-sectional area between the outer surface and the inner surface of hypo-tube 132. Thus, the distance from hypo-tube 132 to any point within the gas fluid path may be relatively small. This may facilitate uniform exposure of the gas to the conductive inner and outer surfaces of hypo-tube 132.

[0045] The shape, length, and / or diameter of the outflow chamber 116 can be selected according to the desired time for the fluid exiting the nozzle 142 to be exposed to the plasma exiting the plasma outflow section 140, for example, to minimize the risk of arc discharge to the surface of, for example, the tissue to be treated. As described above, for example, the outflow chamber 116 can generally have a tubular shape as shown in FIGS. 1 and 2. The wall of the outflow chamber 116 can flare out to allow for a wider spray of the aerosol and plasma. Although not intending to be bound by theory, it is thought that the fine atomization of the liquid within a uniform plasma field can promote the uniformity of the interaction between the plasma and the individual molecules of the liquid. The gas source used to create the aerosol can also be involved in the energy transfer from the plasma. In some embodiments, the high-energy arc associated with the plasma can be fully or partially present within the internal volume defined by the outflow chamber 116. For this reason, there may be insufficient output exiting the outflow chamber 116 for an arc discharge to the tissue of interest. Approaching or contacting the distal end of the outflow chamber 116 with the tissue surface can inhibit the flow of the aerosol and plasma and can act to extinguish the arc at the electrode 130. Referring to FIGS. 3A and 3B, the electrode 130 can communicate with the outflow chamber 116 through an opening 140 within the wall of the chamber 116 that defines the plasma outflow section 140. As shown in FIG. 3B, the opening 140 can be on either side of the nozzle opening 142.

[0046] The adapter 120 can optionally be integrated into the plasma device as a feature. FIG. 4 shows a typical device 200 according to the present disclosure, which includes a body 201, a gas tube 208, a fluid reservoir 210, an actuator 212, an outflow chamber 216, and a cable generator 287. The gas tube 208 can supply gas to the device 200 for generating the aerosol and plasma. The cable generator 287 may provide a power source for generating the plasma. While FIG. 4 shows the gas tube 208 separated from the cable generator 287, in some embodiments, the cable generator 287 can also provide a gas source.

[0047] The device 200 may include any features of the above-described adapter 120 and / or plasma device 180. For example, similar to the nebulizer 106 connected to the adapter 120, the nebulizer 202 of the illustrated device 200 includes an outer compartment 202a, an inner compartment 202b, a needle 203, and a nozzle 204. The outer compartment 202a may receive gas from a gas tube 208, and the inner compartment 202b may receive fluid from a fluid reservoir 210. Thus, the fluid exits the inner compartment 202b above the distal end of the needle 203 and mixes with the gas exiting the outer compartment 202a so that the fluid atomizes and exits through the nozzle 204 as an aerosol into the outflow chamber 216.

[0048] The fluid reservoir 210 shown in FIG. 4 is integrated with the device 200 such that the fluid reservoir 210 is non-removable. In such a case, the fluid reservoir 210 may optionally be configured to allow refilling of the fluid. In other embodiments, the fluid reservoir 210 may be coupled to the device 200 by complementary mating elements such that the fluid reservoir 210 can be refilled or replaced as needed by removing the fluid reservoir 210 from the device 200.

[0049] Once the device 200 is turned on by the actuator 212, gas and current may be supplied to the device 200 simultaneously. The gas may create a pressure differential that draws the fluid from the fluid reservoir 210 to the nebulizer 201 and may atomize the fluid so that the fluid exits through the nozzle 204 and flows into the outflow chamber 216. The gas may also enter the compartment 206 that houses the electrodes and generate plasma within the outflow chamber 216. Thus, for example, current may be supplied to the electrodes 207 to generate plasma within the gas entering the outflow chamber 216 via the plasma outflow portion 205. A typical image of the plasma plume is shown in FIG. 4.

[0050] FIGS. 5A-5E show examples of fluid reservoirs that may be used with the adapter 120, device 200, and any other devices disclosed herein. In some embodiments, the fluid reservoir may be integrated with the device and be similar to the fluid reservoir 210 shown in FIG. 4.

[0051] The fluid reservoirs shown in FIGS. 5A and 5B can be in the form of an injector configured to be connected to the fluid inlet of the device. FIG. 5A shows a fluid reservoir 300 with a tapered adapter 310 configured to be received by the fluid inlet 309 of the device. The upper portion 320 of the fluid reservoir can be openable and closable. For example, the fluid reservoir can be disposable or can have an open top or inlet suitable for introducing additional fluid. For example, FIG. 5B shows a fluid reservoir 400 having an upper portion with a one-way valve 410. Thus, for example, the fluid reservoir 400 can be filled or refilled while avoiding fluid loss, among other things. As shown in FIG. 5B, the fluid inlet 309 of the device may include a mating element 430 complementary to the mating element 420 of the reservoir 400. For example, the complementary mating elements can include threads, luer lock connectors, clips, and the like.

[0052] Referring to FIGS. 5C, 5D, and 5E, the fluid reservoirs suitable for the devices herein can have various shapes other than injectors such as vials, bottles, or tubes. The fluid reservoir 500 of FIG. 5C is shown in the form of a vial 510 having two needles 530, 540 (e.g., two hypodermic needles) configured to enable the release of the vial 510 and the supply of fluid to the device via, for example, a fluid inlet 570 of the device in communication with a nebulizer. When using the two needles 530, 540, atmospheric air or other gas can flow through the fluid channel 520 to the first needle 530, and the fluid in the vial 510 can exit the reservoir 500 through the second needle 540. The vial 510 can also include a vial cap 550 and a stopper 560 to prevent liquid from overflowing, among other things. The vial cap 550 and the stopper 560 can include any suitable material such as rubber or silicon, for example.

[0053] According to some aspects of the present disclosure, a fluid reservoir may be configured to receive and / or transmit data related to the fluid reservoir. For example, FIG. 5D shows a typical fluid reservoir 600 comprising a vial 610 (which may be similar to the vial 510 of FIG. 5C) or other suitable container such as an injector including an electronic chip 620. The electronic chip may comprise one or more sensors configured to collect data and measurements and / or a processor for executing various algorithms. The electronic chip 620 may be disposed outside the fluid reservoir. For example, the vial 610 shown in FIG. 5D may be connected to the inside or inner surface of the fluid reservoir (and may further be electrically insulated from the fluid contained in the fluid reservoir), or may be integrated into the wall of the fluid reservoir. The electronic chip 620 may be programmable to recognize or measure one or more parameters and / or characteristics of the devices or components thereof disclosed herein. Typical parameters may include dosing information (e.g., the number of possible single doses of drug per vial), the type of fluid in the vial, viscosity, temperature, volume, pH, and other characteristics of the fluid in the vial. The fluid reservoir 600 may be electronically connected to the device and / or a generator / power source used with the device to enable data transmission and / or supply of an output to the electronics. In some embodiments, the electronic chip 620 may be configured to receive and / or transmit data.

[0054] The fluid reservoir 700 shown in FIG. 5E comprises a vial 710 (or other suitable type of container) having a fitting element complementary to the fitting element of the fluid inlet 720 of the device. Thus, the fluid reservoir 700 may be selectively connected to and removed from the device. The fluid inlet 720 of the device may comprise a fixture defining a surface 740 that may be tapered to receive the fluid reservoir 700. The surface 740 defines at least one slot 750 or a plurality of slots 750 such that the surface 740 can bend to grip the opening of the vial 710.

[0055] FIG. 5E shows three drawings: a view of vial 710 connected to fluid inlet 720 of the device, a side view of fluid inlet 720 with a function of a fixture including a surface 740 shown by a dotted line and a central fluid channel, and a bottom view of only surface 740 including four slots 750. In some embodiments, surface 740 may comprise only one slot 750, or may comprise two slots 750, three slots 750, or five or more slots 750 that may be arranged at regular intervals along surface 740. The fixture may include a flexible or malleable material such as silicon, rubber, or other flexible polymer, or the slots 750 may provide sufficient clearance or flexibility, and the tapered surface 740 may accommodate and grip vial 710 and may include a harder or semi-rigid material such as plastic to avoid relative movement between fluid inlet 720 and vial 710. In some embodiments, vial 710 may include a function to facilitate a tight grip. For example, vial 710 may comprise a seal 730 for fixing vial 710 to fluid inlet 720 of the device. Vial 710 may be a disposable vial, or may be configured to be refilled and reused.

[0056] The devices described herein may be configured for the treatment of external and / or internal tissue. FIG. 6A shows a typical catheter system 800 for treating internal tissue of a subject. For example, system 800 may be used in endoscopic, cystoscopic, and / or laparoscopic procedures. The illustrated system 800 includes a plasma generator 810, an injector pump 820, and a catheter 830. Plasma generator 810 may be used to supply gas and / or electricity to the catheter. In some embodiments, the gas may be supplied to catheter 830 by a separate gas source independently of plasma generator 810. Injector pump 820 may be any suitable injector system for providing fluid to catheter 830. For example, injector pump 820 may be operated manually or automatically by, for example, a user interface that communicates commands to the electronics of injector pump 820.

[0057] FIG. 6B shows a typical distal end 900 of catheter 830, and FIG. 6C shows an end view of FIG. 6B. As shown in FIG. 6B, catheter 820 may house electrode 910 and nebulizer 920 and may define an outflow chamber 930 at the distal end 900. Nebulizer 920 may include an outer compartment 920a, an inner compartment 920b, and a needle 940 and may be similar to the components of nebulizers 106 and 202 described above that are connected to adapter 120 and device 200. Electrode 910 may be housed within an electrode compartment 912 of catheter 830. Once injector pump 820 is actuated to cause fluid to flow to inner compartment 920b of catheter 830 and plasma generator 810 is turned on to cause gas to flow to outer compartment 920a and electrode compartment 912 to supply electricity to electrode compartment 912, a current generates plasma and aerosol that enters outflow chamber 930. The aerosol exits nebulizer 920 via nozzle 924 and the plasma exits electrode compartment 912 via plasma outflow portion 926.

[0058] Another embodiment of the distal end 950 of catheter 830 of catheter system 800 is shown in FIGS. 7A and 7B. Catheter 830 may include a fluid compartment 970, an electrode 960 housed within an electrode compartment 965, and an outflow chamber 990. The gas and electricity supplied to electrode compartment 965 and electrode 960, respectively, may generate plasma as described above. The plume of plasma may extend at least partially into outflow chamber 990. The distal end of fluid compartment 970 is sealed by a wall 980 that redirects the fluid and passes it through a constricted opening of nozzle 985 to generate an aerosol. Thus, the aerosol contacts the plasma and mixes with the energized species of plasma within outflow chamber 990. FIG. 7B shows an end view of the distal end 950 of catheter 830 including outflow chamber 990 and wall 980.

[0059] The types of catheter system 800 shown in FIGS. 6A-6C and FIGS. 7A-7B can be used in a variety of medical procedures for treating internal tissues, including the above-described endoscopic, cystoscopic, and / or laparoscopic procedures, etc. In at least one embodiment, the catheter system may be used in a tissue removal and / or tissue resection process. For example, a therapeutic agent such as collagen (or any other typical therapeutic agent described herein) can be deposited on the internal tissue surface after tissue removal or resection using the catheter system disclosed herein. In at least one embodiment, cancerous or pre-cancerous tissues (e.g., cancerous or pre-cancerous tissues of the digestive tract such as the esophagus, stomach, intestine, etc.) may be treated with the catheter system disclosed herein.

[0060] Although the principles of the present disclosure are described herein in accordance with exemplary aspects for a particular application, the present disclosure is not limited thereto. Those skilled in the art and users of the description herein will understand additional modifications, uses, aspects, and substitutions of equivalents that are all included within the scope of the aspects described herein. Thus, the present disclosure should not be regarded as limited by the foregoing description.

Claims

1. A medical device comprising: a housing having a nebulizer, wherein the nebulizer has: an outer compartment in communication with a gas inlet; a fluid channel and an inner compartment in communication with a fluid inlet; a needle, wherein the needle is radially inward of the inner compartment, the inner compartment is radially inward of the outer compartment, and a distal end of the outer compartment communicates with a distal end of the inner compartment, the housing comprising the needle; at least one electrode in the form of a pin; a chamber defined by a distal end portion of the housing, wherein a proximal wall of the chamber defines at least one plasma outlet and a nozzle in communication with the nebulizer; the chamber, wherein the pin is proximate to the plasma outlet; the medical device, wherein the proximal wall of the chamber receives an electrode tip of a plasma device and is configured to electrically connect the electrode tip of the plasma device to the at least one electrode.

2. The medical device according to claim 1, wherein a longitudinal position of the needle of the nebulizer is adjustable.

3. The medical device according to claim 1, wherein a distal portion of the housing comprises an actuator configured to control a flow rate of gas to the gas inlet.

4. The medical device according to claim 3, further comprising the plasma device, wherein the actuator of the housing is arranged relative to an actuator of the plasma device such that a user controls a flow rate of gas and simultaneously outputs a supply to the plasma device.

5. The medical device according to claim 1, further comprising a fluid reservoir connected to the fluid inlet.

6. The medical device according to claim 5, wherein the fluid reservoir comprises a fitting element complementary to a fitting element of the fluid inlet such that the fluid reservoir is selectively separable from the fluid inlet.

7. The medical device according to claim 5, wherein the fluid reservoir contains a liquid containing at least one therapeutic agent.

8. The medical device according to claim 7, wherein the at least one therapeutic agent comprises a biomolecule, a pharmaceutical agent, or a combination thereof.

9. The medical device according to claim 7, wherein the at least one therapeutic agent is dissolved in a solvent.

10. The medical device according to claim 1, wherein the housing defines a first channel in communication with the outer compartment of the nebulizer, a second channel including the at least one electrode, and a distal end of the second channel that defines the plasma outflow portion.

11. The medical device according to claim 1, wherein the pin extends into the chamber through the proximal wall of the chamber.

12. A medical device, A housing comprising a nebulizer, the nebulizer comprising An outer compartment, An inner compartment, A needle, The needle is radially inside the inner compartment, the inner compartment is radially inside the outer compartment, and a distal end of the outer compartment communicates with a distal end of the inner compartment, and the housing comprises the needle. A fluid reservoir connected to a fluid inlet and containing a liquid containing at least one therapeutic agent. At least one electrode in the form of a pin. A chamber defined by a distal end portion of the housing, A proximal wall of the chamber defines at least one plasma outflow portion and a nozzle in communication with the nebulizer. The chamber, wherein the pin is proximate to the plasma outflow portion. The medical device, wherein the proximal wall of the chamber receives an electrode tip of a plasma device and is configured to electrically connect the electrode tip of the plasma device to the at least one electrode.

13. The medical device according to claim 12, wherein the fluid reservoir comprises a mating element complementary to a mating element of the fluid inlet such that the fluid reservoir is selectively separable from the fluid inlet.

14. The medical device according to claim 12, wherein the fluid reservoir is permanently installed at the fluid inlet.

15. The medical device according to claim 12, wherein the outer compartment of the nebulizer communicates with a gas inlet, and the inner compartment of the nebulizer communicates with the fluid inlet.

16. The medical device according to claim 12, wherein a distal end of the pin is positioned proximal to the proximal wall of the chamber.

17. The medical device according to claim 12, wherein the housing defines a first channel in communication with the outer compartment of the nebulizer, a second channel including the at least one electrode, and a distal end of the second channel that defines the plasma outflow portion.

18. The medical device according to claim 12, wherein the at least one therapeutic agent comprises a biomolecule, a pharmaceutical agent, or a combination thereof.

19. A medical device, A housing having a nebulizer, wherein the nebulizer comprises An outer compartment in communication with a gas inlet, An inner compartment in communication with a fluid inlet, A needle, The needle is radially inward of each of the inner compartment and the outer compartment, and a distal end of the outer compartment communicates with a distal end of the inner compartment, and a housing comprising the needle, At least one electrode in the form of a pin, A fluid reservoir connected to the fluid inlet, A chamber defined by a distal end portion of the housing, A proximal wall of the chamber defines at least one plasma outflow and a nozzle in communication with the nebulizer, The pin comprises a chamber proximate to the plasma outflow, The proximal wall of the chamber receives an electrode tip of a plasma device and is configured to electrically connect the electrode tip of the plasma device to the at least one electrode. A medical device.

20. The medical device according to any one of claims 1 to 19 for treating a tissue of a subject, wherein the tissue is exposed to a plasma and / or an aerosol containing at least one therapeutic agent using the medical device.

21. The medical device according to claim 20, wherein the tissue is an internal tissue or an external tissue.

22. The medical device according to claim 20, wherein the tissue is a part of a wound, burn, incision, ulcer, abrasion, or tumor.

23. The medical device according to claim 20, wherein the subject is a human subject.

24. The medical device according to claim 20, wherein the plasma is generated at a frequency in the range of about 150 kHz to about 500 kHz.

25. The medical device according to claim 20, wherein the at least one therapeutic agent comprises collagen.

26. The medical device according to claim 20, wherein fluid is supplied to the nebulizer such that the aerosol exits the nozzle simultaneously with the plasma exiting the plasma outflow, and an output is supplied to the at least one electrode simultaneously.

27. The medical device according to claim 26, wherein the fluid is supplied and the output is supplied by pressing a single actuator of the medical device.

28. The medical device according to claim 27, wherein the single actuator is pressed to actuate an output button of the medical device aligned with the single actuator.

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