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 April 3, 2019, the entire contents of which are incorporated herein by reference.

[0002] FIELD OF THE DISCLOSURE The present disclosure relates generally to plasma processing apparatus and methods for using the same. [Background technology]

[0003] Plasma devices are used in medicine for surgical and sterilization procedures. In non-medical industrial applications, plasma devices are used to create thin film coatings, such as polymer coatings. Methods for depositing polymers with plasma devices often rely on the presence of precursors that can react in the plasma to form the polymer coating during the deposition process. These conditions can induce polymerization and can be damaging to various species present in the plasma. Summary of the Invention [Means for solving the problem]

[0004] The present disclosure includes medical devices for generating aerosols and plasmas, such as for therapeutic treatments, including a housing with a nebulizer, the nebulizer having an outer compartment in communication with a gas inlet, an inner compartment in communication with a fluid channel, a fluid inlet, 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 in communication with the distal end of the inner compartment, 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 outlet and a nozzle in communication with the nebulizer, the end of the electrode defining the plasma outlet. Close to , and a chamber.

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

[0006] According to some embodiments of the present disclosure, the medical device may further include a plasma device, wherein an actuator on the housing may be arranged relative to an actuator on the plasma device to allow a user to control the flow rate of gas and simultaneously power the plasma device. In other examples, the medical device may further include a fluid reservoir coupled to the fluid inlet. The fluid reservoir may include a mating element complementary to a mating element on the fluid inlet such that the fluid reservoir is selectively separable from the fluid inlet. In at least one example, the fluid reservoir contains a liquid including at least one therapeutic agent.

[0007] According to some aspects of the present disclosure, the at least one therapeutic agent comprises 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 herein, the housing defines a first channel in communication with an external compartment of the nebulizer, a second channel including an electrode, and a distal end of the second channel defining a plasma outlet, hi at least one embodiment, at least one electrode extends through a wall of the chamber.

[0009] The present disclosure also provides a housing including a nebulizer, the nebulizer comprising 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 being in communication with the distal end of the inner compartment; a fluid reservoir connected to the fluid inlet and containing a liquid including 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 outlet and a nozzle in communication with the nebulizer, the end of the electrode being in communication with the plasma outlet. Close to , a chamber, and a medical device.

[0010] In some embodiments of the present disclosure, the fluid reservoir may include a mating element complementary to a mating element of the fluid inlet such that the fluid reservoir is selectively separable from the fluid inlet. In at least one embodiment, the fluid reservoir is permanently attached to the fluid inlet. In some embodiments, the outer compartment of the nebulizer communicates with the gas inlet, and the inner compartment of the nebulizer communicates with the fluid inlet. In at least one embodiment, an end of the electrode is recessed in a distal-facing surface of the chamber. According to some aspects of the present disclosure, the housing defines a first channel in communication with the outer compartment of the nebulizer, a second channel including the electrode, and a distal end of the second channel defining the plasma outlet. In at least one embodiment, the at least one therapeutic agent includes a biomolecule, a pharmaceutical agent, or a combination thereof.

[0011] The present disclosure also provides a housing comprising a nebulizer, the nebulizer comprising: an outer compartment in communication with a gas inlet; an inner compartment in communication with a fluid channel; and a needle radially inward of each of the inner and outer compartments, the needle being in communication with the distal end of the inner compartment; at least one electrode; a fluid reservoir coupled 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 in communication with the plasma outlet. Close to , a chamber, and a medical device.

[0012] The present disclosure also includes methods of treating tissue in a subject. For example, the methods can include exposing the tissue to plasma and / or an aerosol containing at least one therapeutic agent using any of the medical devices described herein. The tissue can be internal or external. 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 methods include generating plasma at a frequency ranging from about 150 kHz to about 500 kHz.

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

[0014] The method may further include supplying a fluid to the nebulizer and simultaneously powering at least one electrode such that the aerosol exits the nozzle at the same time that the plasma exits the plasma outlet. Supplying the fluid and powering may include depressing a single actuator of the medical device. In at least one embodiment, depressing the single actuator and powering may include depressing a single actuator of the medical device. The present invention provides, for example: (Item 1) A medical device comprising: A housing containing a nebulizer, the nebulizer comprising: an outer compartment in communication with the gas inlet; an interior compartment in communication with the fluid channel and the fluid inlet; A needle, a housing comprising: 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; at least one electrode; a chamber defined by a distal end portion of the housing, a 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 is the plasma outlet. Close to A medical device comprising: a chamber; (Item 2) Item 10. The medical device of item 1, wherein the proximal portion of the chamber is configured to receive an electrode tip of a plasma device and electrically connect the electrode tip of the plasma device to the electrode of the plasma outlet. (Item 3) Item 10. The medical device of item 1, wherein the longitudinal position of the needle of the nebulizer is adjustable. (Item 4) Item 10. The medical device of item 1, wherein the distal portion of the housing comprises an actuator configured to control the flow rate of gas to the gas inlet. (Item 5) 5. The medical device of claim 4, further comprising a plasma device, the actuator of the housing being arranged relative to an actuator of the plasma device so as to allow a user to control the flow rate of gas and power supply to the plasma device simultaneously. (Item 6) Item 10. The medical device of item 1, further comprising a fluid reservoir connected to the fluid inlet. (Item 7) 7. The medical device of claim 6, 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. (Item 8) 7. The medical device of claim 6, wherein the fluid reservoir contains a liquid comprising at least one therapeutic agent. (Item 9) 9. The medical device of claim 8, wherein the at least one therapeutic agent comprises a biomolecule, a pharmaceutical agent, or a combination thereof. (Item 10) 9. The medical device of claim 8, wherein the at least one therapeutic agent is dissolved in a solvent. (Item 11) 2. The medical device of claim 1, wherein the housing defines a first channel in communication with the external compartment of the nebulizer, a second channel including the electrode, and a distal end of the second channel defining the plasma outlet. (Item 12) Item 10. The medical device of item 1, wherein the at least one electrode extends through a wall of the chamber. (Item 13) A medical device comprising: A housing containing a nebulizer, the nebulizer comprising: an exterior compartment; An internal compartment; A needle, a housing comprising: 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; a fluid reservoir connected to the fluid inlet and containing a liquid including at least one therapeutic agent; at least one electrode; a chamber defined by a distal end portion of the housing, a 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 is the plasma outlet. Close to A medical device comprising: a chamber; (Item 14) Item 14. The medical device of item 13, 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. (Item 15) Item 14. The medical device according to item 13, wherein the fluid reservoir is permanently attached to the fluid inlet. (Item 16) Item 14. The medical device of item 13, wherein the outer compartment of the nebulizer is in communication with a gas inlet and the inner compartment of the nebulizer is in communication with the fluid inlet. (Item 17) Item 14. The medical device of item 13, wherein an end of the electrode is recessed in the distal-facing surface of the chamber. (Item 18) Item 14. The medical device of item 13, wherein the housing defines a first channel in communication with the external compartment of the nebulizer, a second channel including the electrode, and a distal end of the second channel defining the plasma outlet. (Item 19) Item 14. The medical device of item 13, wherein the at least one therapeutic agent comprises a biomolecule, a pharmaceutical agent, or a combination thereof. (Item 20) A medical device comprising: A housing containing a nebulizer, the nebulizer comprising: an outer compartment in communication with the gas inlet; an interior compartment in communication with the fluid inlet; A needle, a housing comprising a needle radially inward of each of the inner and outer compartments, the needle being in communication with the distal end of the inner compartment; at least one electrode; a fluid reservoir coupled to the fluid inlet; a chamber defined by a distal end portion of the housing, a 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 is the plasma outlet. Close to A medical device comprising: a chamber; (Item 21) 22. A method of treating tissue of a subject, comprising exposing the tissue to plasma and / or aerosol comprising at least one therapeutic agent using the medical device according to any one of items 1 to 21. (Item 22) 22. The method of claim 21, wherein the tissue is an internal tissue or an external tissue. (Item 23) 22. The method of claim 21, wherein the tissue is part of a wound, burn, incision, ulcer, abrasion, or tumor. (Item 24) 22. The method of claim 21, wherein the subject is a human subject. (Item 25) 22. The method of claim 21, wherein the method comprises generating the plasma at a frequency in the range of about 150 kHz to about 500 kHz. (Item 26) 22. The method of claim 21, wherein the at least one therapeutic agent comprises a biomolecule, a pharmaceutical agent, or a combination thereof. (Item 27) 22. The method of claim 21, wherein the at least one therapeutic agent comprises collagen. (Item 28) 22. The method of claim 21, wherein the method comprises supplying a fluid to the nebulizer and simultaneously powering the at least one electrode such that an aerosol exits the nozzle at the same time that plasma exits the plasma outlet. (Item 29) 29. The method of claim 28, wherein the fluid supplying and power supplying comprise depressing a single actuator of the medical device. (Item 30) 30. The method of claim 29, wherein depressing the single actuator activates an output button of the medical device aligned with the single actuator. [Brief explanation of the drawings]

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

[0016] [Figure 1] FIG. 1 illustrates an exemplary delivery device according to some embodiments of the present disclosure. [Figure 2] FIG. 2 shows a cross-sectional view of the device of FIG. [Figure 3A] 3A and 3B show distal and proximal perspective views, respectively, of the distal end portion of the device of FIG. [Figure 3B] Same as above. [Figure 4] FIG. 4 illustrates another exemplary delivery device according to some embodiments of the present disclosure. [Figure 5A] 5A-5E illustrate exemplary fluid reservoirs according to some embodiments of the present disclosure. [Figure 5B] Same as above. [Figure 5C] Same as above. [Figure 5D] Same as above. [Figure 5E] Same as above. [Figure 6A] FIG. 6A illustrates an exemplary catheter system according to some embodiments of the present disclosure, and FIGS. 6B and 6C illustrate exemplary distal ends of catheters of the system. [Figure 6B] Same as above. [Figure 6C] Same as above. [Figure 7A] 7A and 7B illustrate another exemplary distal end of the catheter system of FIG. 6A according to some embodiments of the present disclosure. [Figure 7B] Same as above. DETAILED DESCRIPTION OF THE INVENTION

[0017] The present disclosure generally includes systems, devices, and methods for delivering active therapeutic agents (e.g., biomolecules, pharmaceutically active agents, and / or combinations thereof) in conjunction with plasma to a surface (e.g., a tissue surface or a non-tissue substrate).

[0018] The singular articles "a," "an," and "the" include plural referents unless the context dictates otherwise. The term "about" indicates approximately the same as a reference number or value. As used herein, the term "about" should generally be understood to encompass ±5% of the particular amount or value. All ranges are understood to include their endpoints, such as, for example, a distance between 1.0 cm and 5.0 cm includes distances of 1.0 cm, 5.0 cm, and all values ​​therebetween.

[0019] The systems and devices herein can be used to apply therapeutic agents to external and / or internal tissues of a subject, such as a human or non-human animal. For example, the therapeutic agents and / or plasma can aid in 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 therapeutic agents before, during, and / or after treating tissue with the plasma. The therapeutic agents can be, for example, incorporated into the plasma, as described further below. Close and / or mixed with an aerosol. In some embodiments, the therapeutic agent comprises one or more pharmaceutical agents and / or biomolecules that do not contain vinyl groups or other chemical functional groups that are expected to polymerize under non-thermal equilibrium plasma conditions. The systems and devices herein may be used to treat a variety of medical conditions, including, but not limited to, internal and / or external burns, wounds, cuts, incisions, ulcers, abrasions, and tumors.

[0020] The plasma may be a 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 supplied at a frequency ranging from about 150 kHz to about 500 kHz, such as from about 200 kHz to about 450 kHz, or from about 150 kHz to about 300 kHz. In some embodiments herein, the maximum frequency may be less than 900 kHz, such as less than 600 kHz or less than 700 kHz. In at least one embodiment, the plasma is pulsed. The plasma may be pulsed at various duty cycles such that the supplied power is less than 100 W, such as less than 20 W or less than 10 W. The applied power may be pulsed such that it is off for at least 50% of the time, e.g., pulsed on and off many times per second. For example, the plasma may be pulsed on and off to provide an on-time ranging from about 1 ns to about 500 ms. For example, the plasma may be pulsed 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, or an on-time of 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. For example, the plasma may be a nanosecond or picosecond pulsed plasma for treating tissue. In these examples, the plasma may be on for only a fraction of a millisecond for each pulse, such as less than 500 ns or less than 100 ns.

[0021] While exemplary devices are described and illustrated herein with particular configurations and components, it will be apparent to those skilled in the art that variations of the devices are also encompassed herein. For example, the components of the devices illustrated may be arranged in a different configuration or omitted entirely. Furthermore, additional components may be added to the devices in light of the teachings herein and in accordance with the principles disclosed.

[0022] 1-3B illustrate features of an exemplary device 100 that can be used to deliver one or more therapeutic agents in conjunction with plasma. For example, FIG. 1 illustrates the device 100 including an adapter 120 coupled to a plasma device 180 for generating non-thermal plasma. The plasma device 180 includes a body with an output button 185 and a distal end portion 184 including a distal tip 182. The distal tip 182 may include an electrode coupled to a power source and a gas source controlled by the output button 185. Thus, activation of the output button 185 of the plasma device 180 initiates simultaneous delivery of gas and alternating current to the distal tip 182, generating plasma. The adapter 120 may be configured to couple to the distal end portion 184 of the plasma device 180, such as in a separable manner. The adapter may enable simultaneous and / or sequential deposition of an aerosol containing one or more therapeutic agents with the plasma generated by the plasma device 180.

[0023] As shown in FIG. 1 , the adapter 120 includes a proximal opening 102 for receiving a distal end portion 184 of a plasma device 180. The adapter 120 can be secured to the plasma device 180 by any suitable connector or mechanism, such as a friction fit (e.g., an inner surface of the proximal opening 102 comprising an elastomeric material), clips, screws, threads, etc. The adapter 120 further includes a distal end portion 104 defining an outlet chamber 116, a nebulizer 106, a gas inlet 108, and a fluid reservoir 110. The gas inlet 108 can be connected to a gas source, such as a medical gas system or a portable cylinder of compressed gas. Typical gases that can 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 fluid reservoir 110 are in communication with the nebulizer 106. Fluid reservoir 110 may be permanently attached to or integral with adapter 120, or fluid reservoir 110 may be connected to adapter 120 by a suitable connector, such as a Luer fitting. In some embodiments herein, fluid reservoir 110 may be in the form of a syringe. Figures 5A-5E show additional examples of fluid reservoirs that may be used in device 100 and / or any other device herein.

[0024] The gas may be regulated at a fixed or variable pressure and / or flow rate. For example, the gas may be regulated 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 may range from about 1 liter per minute (L / min) to about 10 L / min, such as from about 1 L / min to about 5 L / min, from about 5 L / min to about 7 L / min, or from about 4 L / min to about 6 L / min.

[0025] The adapter 120 further includes an actuator 112 configured to control the flow of gas to the nebulizer 106, such as by a valve (which may be mechanical or electrical). Thus, for example, a user can control the flow of gas to the adapter 120 via the actuator 112, which in turn can control the generation of aerosol by the nebulizer 106. That is, when gas begins to flow into the gas inlet 108, the pressure in the nebulizer 106 changes. The fluid contained within the fluid reservoir 110 can be in communication with the nebulizer 106 such that the pressure change draws the fluid from the fluid reservoir 110 into the nebulizer 106. Thus, for example, fluid can be drawn into the nebulizer 106 without an external force or system for pushing the fluid to the nebulizer 106, such as an external pump, liquid delivery system, or external pressurization. That is, the pressure change can be sufficient to draw the fluid from the fluid reservoir 110. The gas and fluid then exit the nebulizer 106 via a nozzle 142 in the distal end portion 104 of the adapter 120. Further details of the nebulizer 106 are shown in FIG.

[0026] 1 , the actuator 112 can be arranged such that when the adapter 120 is coupled to the plasma device 180, the actuator 112 is positioned above the output button 185, allowing a 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 down on the actuator 112 opens a valve to supply gas and also 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 outlets 140.

[0027] According to some embodiments herein, the actuator 112 can be configured to allow a user to separately and independently control the aerosol and 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, sequentially, or simultaneously.

[0028] The fluid reservoir 110 can be open or closed, such as by being capped with a plunger or cap, to prevent fluid from overflowing the fluid reservoir 110. In some embodiments, the fluid reservoir 110 may include a vented plunger or cap, such as to equalize pressure as 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 embodiments of the present disclosure, the fluid reservoir 110 can be positioned at an angle of less than 90 degrees relative to the longitudinal axis of the nebulizer 106. For example, the fluid reservoir 110 can be positioned at an angle ranging from about 10 degrees to about 85 degrees, or from 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 may include any suitable liquid that is compatible with the therapeutic agent and suitable for generating an aerosol. The liquid may include, consist of, or consist essentially of one or more therapeutic agents. The therapeutic agent may be dissolved or otherwise mixed with a solvent, such as water or other aqueous solutions, or alcohol or other organic solvents, among others. Exemplary solvents include, but are not limited to, acetic acid and acetic acid solutions, ethanol and ethanol solutions, water, including acidified water (e.g., pH greater than 3 but less than 7), 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 organic solvents such as alcohols, e.g., methanol, ethanol, propanol, butanol, polyvinyl alcohol, benzoyl alcohol, fatty alcohols, lanolin alcohol, glycerol, ethylene glycol, polyethylene glycol, and mixtures thereof, dimethyl sulfoxide (DMSO), isopropyl myristate, oleic acid, acetone, chloroform, ethyl acetate, azone (laurocapram), urea, essential oils, fatty acids, oxazolidinones, terpenes, terpenoids, and mixtures thereof. Further exemplary organic solvents include organic compounds, e.g., pyrrolidones, e.g., polyvinylpyrrolidone (PVP), cyclodextrins, and the like, dissolved in a suitable liquid, e.g., water or an organic liquid.

[0030] Exemplary therapeutic agents that may be delivered with the devices herein include, but are not limited to, pharmaceutical agents, biomolecules, and mixtures thereof. In some embodiments, the liquid may include one or more pharmaceutically active materials, biomolecules, antibiotics, penetration enhancers, carriers, preservatives, proteins, biopolymers, synthetic biodegradable polymers, or combinations thereof. Exemplary therapeutic agents include, but are not limited to, collagen, fibrin, elastin, fibronectin, hyaluronic acid, chitosan, alginate, cellulose, phosphorylcholine, polypeptides, polyglycans, hormones, lipids, interferon, cartilage, recombinant blood cells, synthetically derived blood cells, platelet-rich plasma, cells (autologous or donor), melanocytes, stem cells, antimicrobial agents, antibiotics, bacteriostatic agents, antibodies (including monoclonal antibodies), stem cells, amniotic membrane material, bovine serum albumin, proteins, clotting factors, growth factors, cytokines, chemotherapeutic agents, anti-inflammatory agents, immunosuppressants, 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, immunosuppressants, angiogenesis inhibitors, vaccines, and combinations thereof. For example, the liquid may contain collagen, plasma, chitosan, or a combination thereof.

[0031] 1 and 2, nebulizer 106 can be any suitable atomizer or nebulizer, including ultrasonic, piezoelectric, pneumatic, mechanical, electrical, vibrating mesh, or jet nebulizers. Nebulizer 106 can include outer section 106a, inner section 106b, needle 107, and threaded connector 107a. Outer section 106a and inner section 106b can be concentric and arranged such that the distal outlet of outer section 106a is in communication with the distal outlet of inner section 106b. Needle 107 can be radially inward of both outer section 106a and inner section 106b, such as being contained within inner section 106b.

[0032] According to some embodiments of the present disclosure, the fluid reservoir 110 can be located relatively close to the nebulizer. For example, the fluid reservoir 110 can be located less than about 50 mm, such as about 1 mm to about 50 mm, from the nebulizer 106. For example, the fluid reservoir 110 can be located 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 intending to be bound by theory, it is believed that locating the fluid reservoir 110 relatively close to the nebulizer 106 can efficiently transport fluid. For example, fluid may be supplied to the nebulizer without a syringe pump or tubing or other fluid lines.

[0033] The external compartment 106a may be in communication with a gas source, and the internal compartment 106b may be in communication with a fluid source. For example, as shown in FIG. 2, a gas inlet 108 connects a gas source to the external compartment 106a of the adapter 120 such that gas passes through the gas inlet 108 and is supplied to the external compartment 106a of the nebulizer 106. Similarly, a fluid inlet 109 connects a fluid source (e.g., fluid reservoir 110) to the internal compartment 106b. As described above, fluid contained in the fluid reservoir 110 may enter a fluid channel that is in communication with the internal compartment 106b of the nebulizer 106. Thus, for example, when gas flow is on, pressure changes within the adapter 120 may draw fluid from the fluid reservoir 110 into the internal compartment 106b. The gas and fluid then exit the distal outlets of the outer and inner compartments 106a, 106b as aerosols via a nozzle 142 in the distal end portion 104 of the adapter 120. Upon exiting the nozzle 142, the aerosol is introduced into the outlet chamber 116 so that the aerosol can mix with the plasma entering the chamber 116 via a plasma outlet 140 adjacent the nozzle 142 before contacting the surface to be treated with the plasma and therapeutic agent. The outlet chamber 116 can have dimensions that define a volume sufficient for the aerosol to mix with the plasma before deposition on the surface, such as the tissue to be treated. The outlet chamber 116 can have various shapes, such as a conical shape that can flare out at the distal end such that the cross-sectional dimension of the distal end of the chamber 116 is greater than the cross-sectional dimension of the proximal end of the chamber 116. The flared conical shape can allow the plasma and aerosol to exit and cover a relatively large surface area to be treated. In some embodiments, the chamber 116 can narrow at its distal end, for example, to allow a more targeted or focused flow of the aerosol and plasma onto the surface being treated. According to some aspects of the present disclosure, the length of the chamber ranges from about 10 mm to about 100 mm, such as from about 30 mm to about 50 mm, or from about 35 mm to about 45 mm. Further, for example, the chamber can have a cross-sectional shape with an inner diameter ranging from about 6 mm to about 50 mm, such as from about 10 mm to about 30 mm, or from about 15 mm to about 25 mm.

[0034] In the embodiment of the present disclosure, the outer section 106a and the inner section 106b are connected to the nozzle 142. in or In close proximity to The tip of the needle 107 may be tapered toward the nozzle 142. In some embodiments, the tip of the needle 107 may be flush with the proximal wall of the outflow chamber 116, or the tip may protrude into the outflow chamber 116. In either case, the tip of the needle 107 may be positioned relative to the nozzle 142 to allow the aerosol to enter the chamber 116.

[0035] Without intending to be bound by theory, it is believed that the reduced radial cross-section of the outer and inner compartments 106a, 106b may accelerate the flow of gas and liquid, thereby reducing pressure. This pressure change imparts a Venturi effect to the inner compartment 106b, causing the pressure to be lower at the distal outlet 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. As the liquid exits the inner compartment 106b over the tip of the needle 107, it can be atomized by gas passing through the nozzle 142 and exiting the outer compartment 106a, creating an aerosol in the outlet chamber 116.

[0036] In some embodiments of the present disclosure, the distal end of the external compartment 106a communicates with the distal end of the internal compartment 106b via an opening having a circular annular shape. For example, the opening may have a uniform circular annular shape, such that a uniform flow of gas exits the external compartment 106a, contacts the liquid from the internal compartment 106b, and then passes through the nozzle 142 and exits 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 the resulting shape and / or volume of the spray. For example, a flat orifice can produce a fan-shaped spray. In embodiments of the present disclosure, the atomized fluid spray has a uniform conical shape. Furthermore, reducing the annular distance between the inner diameter of the external compartment 106a and the outer diameter of the internal compartment 106b can increase the velocity of the gas exiting the distal end of the external compartment 106a. The increased gas flow rate is expected to further reduce the pressure at the distal end of the internal compartment 106b.

[0037] According to some embodiments of the present disclosure, a uniform annular opening is provided between the internal compartment 106b and the tip of the needle 107. The size of the annular opening can limit the amount of fluid that exits the distal end of the internal compartment 106b. Without intending to be bound by theory, the orientation of the distal end of the needle 107, the internal compartment 106b, and the external compartment 106a can characterize the performance of the nozzle 142 in generating an aerosol. The external compartment 106a may have a nozzle throat corresponding to the smallest diameter portion of the distal end of the external compartment 106a. The dimensions of the throat relative to the rest of the nozzle 142 and the pressure of the incoming gas can determine the pressure within the nozzle 142 and, therefore, the strength of the Venturi effect. The distal end of the internal compartment 106b may be spaced apart from the nozzle throat portion of the external compartment 106a such that the pressure at the nozzle throat is lower than the pressure in the fluid reservoir 110. to Or Close to, or outside the nozzle throat of the outer compartment 106a. Otherwise, the pressure within the nozzle may be above atmospheric pressure, preventing fluid from flowing from the fluid reservoir 110 to the inner compartment 106b; instead, gas may flow into the fluid reservoir 110. The distal end of the inner compartment 106b may also be sufficiently close to the distal end of the outer compartment 106a so that the gas flow may 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 coupler 107a of the nebulizer 106 can be attached to or integral with the proximal end of the needle 107, and the threaded coupler 107a can mate with internal threads in the proximal portion of the internal compartment 106b. The needle 107 can be retracted or advanced by rotating the threaded coupler 107a, thereby increasing or decreasing the aerosol flow from the nozzle 142. The threaded coupler 107a can be fixed or adjustable. In embodiments of the present disclosure, the needle 107 can be advanced and seated against the inner surface of the distal end of the internal compartment 106b. Further advancement of the needle 107 can result in a slight deformation of the distal end of the internal compartment 106b, positioning the distal end within the distal end of the external compartment 106a. Retracting the needle 107 establishes an annular space between the needle 107 and the distal end of the internal compartment 106b, regulating the fluid path and the generation of aerosol through the nozzle 142.

[0039] The needle 107 may comprise any suitable material or combination of materials. Typical materials useful for the needle 107 include, but are not limited to, metals and metal alloys, such as stainless steel. As the fluid exits the distal end of the inner compartment 106b over the surface of the needle 107, it is atomized by the flow of gas from the distal end of the outer 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 its position relative to the distal ends of the respective outer and inner compartments 106a and 106b. The shape of the nebulizer 106 and / or nozzle 142 may be configured to provide a desired spray radius and 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 needle 107 and the distal end of interior compartment 106b can range from about 5 mm to about 60 mm, such as from about 15 mm to about 25 mm, or from about 15 mm to about 25 mm.

[0040] The surface of the needle 107 may be sufficiently smooth so that the fluid flows evenly over the surface and atomizes the fluid evenly. For example, the surface of the needle may be smoothed, such as by grinding or a similar process. In some embodiments, the needle 107 may have a surface that is polished with 800 grit abrasive.

[0041] 3A and 3B show distal and proximal perspective views, respectively, of the outflow chamber 116. As shown, the proximal side of the outflow chamber 116 can include a hypotube 132, at least two electrodes 130, and a proximally extending housing 136 that surrounds the nebulizer 106. The hypotube 132 can be a tubular structure configured to receive the distal tip 182 of the plasma device 180, optionally with a beveled tip. In some embodiments, the hypotube 132 is coupled to the chamber 116 by an adhesive, such as a light-curable adhesive. The hypotube 132 can comprise any suitable material, such as a metal or metal alloy.

[0042] The hypotube 132 may be in communication with the electrodes 130, such as by a conductive wire. The electrodes 130 may be separately housed in tubing, which may be connected, for example, proximal to the outflow chamber 116, by a suitable mounting structure. In some embodiments, the adapter 120 may include only one electrode 130 or more than three electrodes 130. For example, the adapter 120 may include three or more electrodes 130, such as arranged in a ring. As described above, the hypotube 132 may be connected to each of the electrodes 130 by a conductive material, such as copper wire, which may be surrounded by an insulating material, such as a polymer coating. The insulated wire may be coupled to the hypotube 132 and secured in place by an insulating material, such as a silicone tubing sleeve. The silicone tubing sleeve and light-cured adhesive may electrically insulate the hypotube 132 and the electrodes 130, minimizing electrical energy loss at the junction of each electrode 130. The electrodes 130 may be housed in a suitable insulating material, such as plastic or silicone.

[0043] In some embodiments of the present disclosure, electrode 130 may include a pin that may be flush with the wall of effluent chamber 116 and may be recessed or protrude into effluent chamber 116. In at least one embodiment, the pin of electrode 130 is recessed or protrudes into chamber 116 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 intending to be bound by theory, it is believed that having the pin of electrode 130 recessed into chamber 116 may increase the intensity of the plasma discharge.

[0044] In some embodiments, the hypotube 132 may have an inner cross-sectional area that is approximately the same as the outer annular cross-sectional area between the outer surface of the hypotube 132 and the inner surface of the hypotube 132 passing through the effluent chamber 116. Thus, the distance from the hypotube 132 to any point in the gas fluid path may be relatively small. This may promote uniform exposure of the gas to the conductive inner and outer surfaces of the hypotube 132.

[0045] The shape, length, and / or diameter of the effluent chamber 116 can be selected according to the desired exposure time of the fluid exiting the nozzle 142 to the plasma exiting the plasma outlet 140 to minimize the risk of arcing to a surface, such as the tissue being treated. As described above, for example, the effluent chamber 116 can have a generally tubular shape, as shown in FIGS. 1 and 2 . The walls of the effluent chamber 116 can flare to create a wider aerosol and plasma spray. Without intending to be bound by theory, it is believed that fine atomization of the liquid within a uniform plasma field can promote uniform interaction between the plasma and individual molecules of the liquid. The gas source used to create the aerosol can also contribute to the transfer of energy from the plasma. In some embodiments, the high-energy arc associated with the plasma can reside fully or entirely within the internal volume defined by the effluent chamber 116. As a result, there may be insufficient power exiting the effluent chamber 116 to arc to the target tissue. Bringing the distal end of the effusion chamber 116 close to or in contact with the tissue surface may disrupt the flow of aerosol and plasma and act to extinguish the arc at the electrode 130. With reference to Figures 3A and 3B, the electrode 130 may communicate with the effusion chamber 116 through an opening 140 in the wall of the chamber 116, which defines a plasma outlet 140. As shown in Figure 3B, the opening 140 may be on either side of a nozzle opening 142.

[0046] Features of the adapter 120 may optionally be integrated into the plasma device. FIG. 4 shows an exemplary device 200 according to the present disclosure, including a body 201, a gas conduit 208, a fluid reservoir 210, an actuator 212, an outflow chamber 216, and a cable generator 287. The gas conduit 208 may supply gas to the device 200 for generating the aerosol and plasma. The cable generator 287 may provide a power source to generate the plasma. While FIG. 4 shows the gas conduit 208 separate from the cable generator 287, in some embodiments, the cable generator 287 may also provide a gas source.

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

[0048] 4 is integrated into the device 200 such that the fluid reservoir 210 is non-removable. In such cases, the fluid reservoir 210 may optionally be configured to allow for refilling with 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 may be refilled or replaced as needed by removing the fluid reservoir 210 from the device 200.

[0049] Once device 200 is turned on by actuator 212, gas and electrical current may be simultaneously supplied to device 200. The gas may create a pressure differential that draws fluid from fluid reservoir 210 into nebulizer 201, atomizing the fluid as it flows out nozzle 204 and into outlet chamber 216. The gas may also enter compartment 206, which houses an electrode, generating a plasma within outlet chamber 216. Thus, for example, electrical current may be supplied to electrode 207, generating a plasma within the gas entering outlet chamber 216 via plasma outlet 205. A typical image of a plasma plume is shown in FIG. 4.

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

[0051] The fluid reservoir shown in FIGS. 5A and 5B can be in the form of a syringe configured to connect to a fluid inlet of a device. FIG. 5A shows a fluid reservoir 300 with a tapered adapter 310 configured to be received by the fluid inlet 309 of a device. The top 320 of the fluid reservoir can be openable. 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 in which the top of the reservoir 400 includes a one-way valve 410. This allows the fluid reservoir 400 to be filled or refilled with fluid, for example, while avoiding fluid loss. As shown in FIG. 5B, the fluid inlet 309 of the device can include a mating element 430 complementary to the mating element 420 of the reservoir 400. For example, the complementary mating element can include a thread, a luer lock connector, a clip, or the like.

[0052] 5C, 5D, and 5E, fluid reservoirs suitable for the devices herein can have various shapes other than syringes, such as vials, bottles, or tubes. The fluid reservoir 500 in FIG. 5C is shown in the form of a vial 510 with two needles 530, 540 (e.g., two hypodermic needles) configured to allow for the discharge of the vial 510 and the delivery of fluid to the device, such as via a fluid inlet 570 of the device in communication with a nebulizer. When two needles 530, 540 are used, air or other gas at atmospheric pressure can flow through the fluid channel 520 into the first needle 530, and fluid within 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, such as to prevent overflow of liquid. Vial cap 550 and stopper 560 may comprise any suitable material, such as, for example, rubber or silicone.

[0053] According to some embodiments of the present disclosure, a fluid reservoir can be configured to receive and / or transmit data related to the fluid reservoir. For example, FIG. 5D shows an exemplary fluid reservoir 600 comprising a vial 610 (which may be similar to vial 510 in FIG. 5C) or other suitable container, such as a syringe, containing 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 located external to the fluid reservoir; for example, the vial 610 shown in FIG. 5D may be coupled to the interior or inner surface of the fluid reservoir (and may be electrically isolated from the fluid contained therein), 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 disclosed herein or their components. Typical parameters may include dosing information (e.g., number of possible drug doses administered per vial), type of fluid in the vial, viscosity, temperature, volume, pH, and other characteristics of the fluid in the vial. Fluid reservoir 600 may be electronically coupled to the device and / or generator / power source used in the device to allow transmission of data and / or power supply to electronic components. In some embodiments, electronic chip 620 may be configured to receive and / or transmit data.

[0054] 5E includes a vial 710 (or other suitable type of container) with a mating element complementary to a mating element of a fluid inlet 720 of the device. This allows the fluid reservoir 700 to be selectively coupled to and detached from the device. The fluid inlet 720 of the device may include a fastener defining a surface 740, which may be tapered, for receiving the fluid reservoir 700. The surface 740 defines at least one slot 750 or multiple slots 750 that allow the surface 740 to flex and grip the opening of the vial 710.

[0055] 5E shows three views: a diagram of a vial 710 coupled to a fluid inlet 720 of a device; a side view of the fluid inlet 720 with a fastener feature including a surface 740 and a central fluid channel shown in dotted lines; and a top-down view of only the surface 740, which includes four slots 750. In some embodiments, the surface 740 may include only one slot 750, or may include two slots 750, three slots 750, or five or more slots 750, which may be spaced at regular intervals along the surface 740. The fastener may include a flexible or malleable material such as silicone, rubber, or other flexible polymer, or may include a more rigid or semi-rigid material such as plastic, where the slots 750 provide sufficient clearance or flexibility and the tapered surface 740 can accommodate and grip the vial 710 while preventing relative movement between the fluid inlet 720 and the vial 710. In some embodiments, vial 710 may include features to facilitate a tight grip. For example, vial 710 may include a seal 730 to secure vial 710 to the 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 herein may be configured for treating external and / or internal tissue. FIG. 6A illustrates an exemplary catheter system 800 for treating internal tissue of a subject. For example, the 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. The plasma generator 810 may be used to supply gas and / or electricity to the catheter. In some embodiments, gas may be supplied to the catheter 830 by a separate gas source, independent of the plasma generator 810. The injector pump 820 may be any suitable injector system for providing fluid to the catheter 830. For example, the injector pump 820 may be operated manually or automatically, such as by a user interface that communicates commands to the electronics of the injector pump 820.

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

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

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

[0060] While the principles of the present disclosure have been described herein with reference to illustrative embodiments for particular applications, the present disclosure is not limited thereto. Those skilled in the art and those using the teachings herein will recognize additional modifications, applications, embodiments, and equivalent substitutions that are all within the scope of the embodiments described herein. Thus, the present disclosure is not to be deemed limited by the foregoing description.

Claims

1. A medical device comprising: A housing containing a nebulizer, the nebulizer comprising: an outer compartment in communication with the gas inlet; an interior compartment in communication with the fluid channel and the fluid inlet; A needle, a housing comprising: 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; 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 defining at least one plasma outlet and a nozzle in communication with the nebulizer; the pin includes a chamber adjacent to the plasma outlet; The medical device, wherein the proximal wall of the chamber is configured to receive an electrode tip of a plasma device and electrically connect the electrode tip of the plasma device to the at least one electrode.

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

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

4. 4. The medical device of claim 3, further comprising the plasma device, wherein the actuator of the housing is arranged relative to an actuator of the plasma device to allow a user to simultaneously control gas flow and power delivery to the plasma device.

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

6. The medical device of claim 5 , 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.

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

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

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

10. 2. The medical device of claim 1, wherein the housing defines a first channel in communication with the external compartment of the nebulizer, a second channel including the at least one electrode, and a distal end of the second channel defining the plasma outlet.

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

12. A medical device comprising: A housing containing a nebulizer, the nebulizer comprising: an exterior compartment; An internal compartment; A needle, a housing comprising: 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; a fluid reservoir connected to the fluid inlet and containing a liquid including 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 defining at least one plasma outlet and a nozzle in communication with the nebulizer; the pin includes a chamber adjacent to the plasma outlet; The medical device, wherein the proximal wall of the chamber is configured to receive an electrode tip of a plasma device and electrically connect the electrode tip of the plasma device to the at least one electrode.

13. 13. The medical device of 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 of claim 12 , wherein the fluid reservoir is permanently attached to the fluid inlet.

15. 13. The medical device of claim 12, wherein the outer compartment of the nebulizer is in communication with a gas inlet and the inner compartment of the nebulizer is in communication with the fluid inlet.

16. A medical device as described in claim 12, wherein the distal end of the pin is positioned proximal to the proximal wall of the chamber.

17. 13. The medical device of claim 12, wherein the housing defines a first channel in communication with the external compartment of the nebulizer, a second channel including the at least one electrode, and a distal end of the second channel defining the plasma outlet.

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

19. A medical device comprising: A housing containing a nebulizer, the nebulizer comprising: an outer compartment in communication with the gas inlet; an interior compartment in communication with the fluid inlet; A needle, a housing comprising a needle radially inward of each of the inner and outer compartments, the needle being in communication with the distal end of the inner compartment; at least one electrode in the form of a pin; a fluid reservoir coupled to the fluid inlet; a chamber defined by a distal end portion of the housing, a proximal wall of the chamber defining at least one plasma outlet and a nozzle in communication with the nebulizer; the pin includes a chamber adjacent to the plasma outlet; The medical device, wherein the proximal wall of the chamber is configured to receive an electrode tip of a plasma device and electrically connect the electrode tip of the plasma device to the at least one electrode.

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

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

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

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

24. 21. The medical device of claim 20, wherein the plasma is generated at a frequency ranging from about 150 kHz to about 500 kHz.

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

26. 21. The medical device of claim 20, wherein a fluid is supplied to the nebulizer and power is supplied to the at least one electrode simultaneously such that an aerosol exits the nozzle at the same time that plasma exits the plasma outlet.

27. 27. The medical device of claim 26, wherein the fluid is delivered and the output is delivered by depressing a single actuator of the medical device.

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

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