Plasma processing apparatus and method of using the same

Abstract

Describes a medical device for generating aerosols and plasmas, for example, for therapeutic treatment. The medical device may include a nebulizer that includes an outer chamber, an inner chamber, and a needle located radially inside the inner and outer chambers. The medical device may include at least one electrode and a chamber, wherein the distal-facing surface of the chamber defines at least one plasma outlet and a nozzle in communication with the nebulizer, and the end of the electrode is close to the plasma outlet.

Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit of priority to U.S. Provisional Application No. 62 / 828,797, filed on April 3, 2019, the entire content of which is incorporated herein by reference. Technical Field

[0003] The present disclosure generally relates to plasma processing apparatuses and methods of using the same. Background Art

[0004] Plasma devices are used medically in surgical and disinfection techniques. Outside of medicine, in industrial applications, plasma devices are used to produce thin film coatings, such as polymer coatings. Methods of depositing polymers with plasma devices typically rely on the presence of precursors that can react in the plasma during deposition to form a polymer coating. Such conditions may initiate polymerization but also break down various substances present in the plasma. Summary of the Invention

[0005] The present disclosure includes a medical device for generating an aerosol and a plasma, e.g., for therapeutic treatment. For example, the medical device may include a housing that includes an atomizer that includes an outer chamber in communication with a gas inlet, an inner chamber in communication with a fluid passage and a fluid inlet, and a needle, where the needle is radially interior to the inner chamber, the inner chamber is radially interior to the outer chamber, and a distal end of the outer chamber is in communication with a distal end of the inner chamber; at least one electrode; and a chamber defined by a distal portion of the housing, where a distal-facing surface of the chamber defines at least one plasma outlet and a nozzle in communication with the atomizer; and where an end of the electrode is proximate to the plasma outlet.

[0006] In an example herein, a proximal portion of the chamber may be configured to receive an electrode tip of a plasma device and electrically connect the electrode tip of the plasma device to an electrode of the plasma outlet, and / or a distal portion of the housing may include an actuator configured to control a flow of gas to the gas inlet. A longitudinal position of the needle of the atomizer is adjustable.

[0007] According to some embodiments of the present disclosure, the medical device may further include a plasma device, where an actuator of the housing may be arranged relative to an actuator of the plasma device to allow a user to control a flow 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 of the fluid inlet such that the fluid reservoir can be selectively detached from the fluid inlet. In at least one example, the fluid reservoir houses a liquid that includes at least one therapeutic agent.

[0008] According to some aspects of the present disclosure, at least one therapeutic agent includes a biomolecule, a medicament, or a combination thereof. In some examples, at least one therapeutic agent is dissolved in a solvent.

[0009] In some examples herein, the housing defines a first channel in communication with the outer chamber of the nebulizer and a second channel housing an electrode, and the distal end of the second channel defines a plasma outlet. In at least one example, at least one electrode extends through the wall of the chamber.

[0010] The present disclosure also includes a medical device that includes a housing that includes a nebulizer that includes an outer chamber, an inner chamber, and

[0011] a needle, where the needle is radially interior to the inner chamber, the inner chamber is radially interior to the outer chamber, and the distal end of the outer chamber is in communication with the distal end of the inner chamber; a fluid reservoir coupled to the fluid inlet that houses a liquid including at least one therapeutic agent; at least one electrode; and a chamber defined by a distal portion of the housing, where the distal-facing surface of the chamber defines at least one plasma outlet and a nozzle in communication with the nebulizer; and where the end of the electrode is proximate to the plasma outlet.

[0012] In some embodiments of the present disclosure, the fluid reservoir may include a mating element complementary to the mating element of the fluid inlet such that the fluid reservoir can be selectively detached from the fluid inlet. In at least one example, the fluid reservoir is permanently attached to the fluid inlet. In some examples, the outer chamber of the nebulizer is in communication with a gas inlet and the inner chamber of the nebulizer is in communication with the fluid inlet. In at least one example, the end of the electrode is recessed from the 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 chamber of the nebulizer and a second channel housing an electrode, and the distal end of the second channel defines a plasma outlet. In at least one example, at least one therapeutic agent includes a biomolecule, a medicament, or a combination thereof.

[0013] The present disclosure also includes a medical device that includes a housing that includes a nebulizer that includes an outer chamber in communication with a gas inlet, an inner chamber in communication with the fluid inlet, and a needle, where the needle is radially interior to each of the inner chamber and the outer chamber, and the distal end of the outer chamber is in communication with the distal end of the inner chamber; at least one electrode; a fluid reservoir coupled to the fluid inlet; and a chamber defined by a distal portion of the housing, where the distal-facing surface of the chamber defines at least one plasma outlet and a nozzle in communication with the nebulizer; and where the end of the electrode is proximate to the plasma outlet.

[0014] The present disclosure also includes methods of treating a subject's tissue. 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 examples, the tissue can be part of a wound, burn, cut, ulcer, abrasion, or tumor. In at least one example, the subject is a human subject. In some examples, the method includes generating a plasma at a frequency in the range from about 150 kHz to about 500 kHz.

[0015] According to some aspects of the present disclosure, the at least one therapeutic agent includes a biomolecule, a drug, or a combination thereof. In some examples, the at least one therapeutic agent comprises collagen.

[0016] The method can further include simultaneously supplying fluid to a nebulizer and supplying power to at least one electrode such that the aerosol exits the nozzle while the plasma exits the plasma outlet. Supplying the fluid and supplying the power can include pressing a single actuator of the medical device. In at least one example, pressing the single actuator and supplying the power can include pressing a single actuator of the medical device. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The drawings incorporated in and forming a part of this specification illustrate certain features of the present disclosure and, together with the description, are used to explain the principles of the present disclosure. Those of ordinary skill in the art will readily recognize that the features of a particular aspect or embodiment can be combined with the features of any or all of the other aspects or embodiments described in the present disclosure.

[0018] Figure 1 An exemplary delivery device is shown in accordance with some aspects of the present disclosure.

[0019] Figure 2 is shown Figure 1 a cross-sectional view of the device.

[0020] Figure 3A and 3B respectively show Figure 1 a distal and a proximal perspective view of the distal portion of the device.

[0021] Figure 4 Another exemplary device is shown in accordance with some aspects of the present disclosure.

[0022] Figures 5A - 5E An exemplary fluid reservoir is shown in accordance with some aspects of the present disclosure.

[0023] Figure 6A An exemplary catheter system is shown in accordance with some aspects of the present disclosure, Figure 6B and 6C shows an exemplary distal end of the catheter of the system.

[0024] Figure 7A and 7B shows another exemplary distal end of a catheter system in accordance with some aspects of the present disclosure. Figure 6A Detailed Description

[0025] 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).

[0026] Unless the context dictates otherwise, the singular forms "a," "an," and "the" include plural referents. The terms "about" and "approximately" refer to being nearly the same as the recited number or value. As used herein, the terms "about" and "approximately" generally should be understood to encompass ±5% of the specified amount or value. All ranges are understood to include the endpoints, e.g., a distance between 1.0 cm and 5.0 cm includes the distance of 1.0 cm, the distance of 5.0 cm, and all values therebetween.

[0027] 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 non-human animal. For example, the therapeutic agent and / or plasma can aid in healing. The systems and devices herein can be configured to deliver one or more therapeutic agents in and / or adjacent to plasma and can be configured to deliver the therapeutic agent before, during, and / or after treating the tissue with plasma. The therapeutic agent can be delivered, for example, via an aerosol that is proximal to and / or mixed with plasma, as further described below. In some embodiments, the therapeutic agent includes one or more drugs and / or biomolecules that do not contain vinyl or other chemical functional groups that are expected to polymerize under non-thermal equilibrium plasma conditions. The systems and devices herein can 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.

[0028] ​The plasma can be non-thermal equilibrium or cold plasma, e.g., to minimize damage to the therapeutic agent, tissue damage, and / or subject discomfort. For example, the plasma can be powered at a frequency in the range 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 examples herein, the maximum frequency can be less than 900 kHz, such as less than 700 kHz, e.g., less than 600 kHz. In at least one aspect, the plasma is pulsed plasma. The plasma can be pulsed at various duty cycles such that the delivered power is less than 100 W, e.g., less than 20 W or less than 10 W. The pulse can be such that the applied electrical power is off at least 50% of the time, e.g., the pulse is turned on and off multiple times per second. For example, the plasma can be pulsed on and off to deliver an on-time in the range from about 1 ns to about 500 ms. For example, the plasma can be pulsed with an on-time of 1 ms to 500 ms, such as 10 ms to 300 ms, 50 ms to 100 ms, e.g., 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, for the treatment of tissue, the plasma can be nanosecond or picosecond pulsed plasma. In these examples, for each pulse, the plasma can be on for only a fraction of a millisecond, e.g., less than 500 ns or less than 100 ns.

[0029] While exemplary devices are described herein and illustrated with given configurations and components, it will be apparent to those of ordinary skill in the art that variations of these devices are also covered herein. For example, the components of the devices shown in the figures can be arranged in different configurations or can be omitted altogether. Further, additional components can be added to the devices in view of the discussion herein and in accordance with the disclosed principles.

[0030] Figures 1 - 3B Features of an exemplary device 100 that can be used to deliver one or more therapeutic agents in combination with a plasma are shown. For example, Figure 1FIG. 0 shows an apparatus 100 that includes an adapter 120 coupled to a plasma device 180 for generating non-thermal plasma. The plasma device 180 includes a body with a power button 185 and a distal portion 184 that includes a distal tip 182. The distal tip 182 may include an electrode coupled to a power source and a gas source controlled by the power button 185. Thus, engaging the power button 185 of the plasma device 180 initiates the simultaneous delivery of gas and alternating current to the distal tip 182 to generate plasma. The adapter 120 may be configured to couple to the distal portion 184 of the plasma device 180 in a detachable manner, for example. The adapter may allow for the simultaneous and / or sequential deposition of an aerosol containing one or more therapeutic agents with the plasma generated by the plasma device 180.

[0031] As Figure 1 shown in FIG. 5, the adapter 120 includes a proximal opening 102 for receiving the distal portion 184 of the plasma device 180. The adapter 120 may be secured to the plasma device 180 via any suitable connection or mechanism (e.g., friction fit (e.g., the inner surface of the proximal opening 102 includes an elastic material), clip, screw, threads, etc.). The adapter 120 further includes a distal portion 104 that defines an exit chamber 116, an atomizer 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 compressed gas cylinder. Exemplary gases that may be used with the devices and systems herein include, but are not limited to, air (including medical gas), nitrogen, helium, argon, and mixtures thereof. The gas inlet 108 and the fluid reservoir 110 are in communication with the atomizer 106. The fluid reservoir 110 may be permanently attached to the adapter 120, or integrally formed therewith, or the fluid reservoir 110 may be coupled to the adapter 120 via a suitable connector such as a Luer fitting. In some examples herein, the fluid reservoir 110 may be in the form of a syringe. Figures 5A - 5E FIG. 7 shows additional examples of fluid reservoirs that may be used with the apparatus 100 and / or any other device herein.

[0032] The gas may be regulated at a fixed or variable pressure and / or flow rate. For example, the gas may be regulated to be at a pressure of about 30 psi to about 40 psi, such as about 35 psi. In some embodiments of the present disclosure, the gas flow rate for generating plasma may be in the range of 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.

[0033] The adapter 120 further includes an actuator 112 configured to control the airflow to the atomizer 106, for example, via a valve (which can be mechanical or electrical). Thus, for example, a user can control the airflow to the adapter 120 via the actuator 112, which in turn can control the generation of the aerosol via the atomizer 106. That is, initiating the flow of gas to the gas inlet 108 results in a pressure change in the atomizer 106. The fluid contained within the fluid reservoir 110 can be in communication with the atomizer 106 such that the pressure change draws the fluid from the fluid reservoir 110 into the atomizer 106. Thus, for example, the fluid can be drawn into the atomizer 106 without an external force or system (such as an external pump, a liquid delivery system, or external pressurization) pushing the fluid into the atomizer 106. That is, the pressure change may be sufficient to aspirate the fluid from the fluid reservoir 110. The gas and fluid then exit the atomizer 106 via the nozzle 142 of the distal portion 104 of the adapter 120. Figure 2 Further details of the atomizer 106 are shown.

[0034] Further reference Figure 1 to, the actuator 112 can be arranged such that when the adapter 120 is coupled to the plasma device 180, the actuator 112 is superimposed over the power button 185 to allow the user to generate the aerosol and the plasma simultaneously. Thus, for example, once the plasma device 180 is engaged with the adapter 120 (e.g., the distal portion 184 of the plasma device 180 is inserted into the proximal opening 102 of the adapter 120), pressing the actuator 112 can open the valve of the gas supply and also engage the power 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.

[0035] According to some examples herein, the actuator 112 can be configured to allow the user to control the aerosol and the plasma separately and independently. For example, the actuator 112 can include a first portion that engages the valve of the gas supply and a second portion that engages the power button 185, where the first portion and the second portion can be pressed separately, sequentially, or simultaneously.

[0036] The fluid reservoir 110 can be open or closed, such as having a plunger or lid on top to prevent fluid from spilling out of the fluid reservoir 110. In some examples, the fluid reservoir 110 can include a plunger or lid that provides venting, for example, to equalize pressure as the liquid exits. The fluid reservoir 110 can be coupled to the atomizer 106 at an appropriate angle to allow the fluid contained within the fluid reservoir 110 to flow by gravity into a channel that communicates with the atomizer 106. According to some aspects of the present disclosure, the fluid reservoir 110 can be positioned at an angle less than 90 degrees relative to the longitudinal axis of the atomizer 106. For example, the fluid reservoir 110 can be at an angle in the range from 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.

[0037] The fluid contained within the fluid reservoir 110 can include any suitable liquid that is compatible with the therapeutic agent and is suitable for generating an aerosol. The liquid can include, consist of, or consist essentially of one or more therapeutic agents. In other examples, the therapeutic agent can be dissolved or otherwise mixed with a solvent, such as water or other aqueous solutions, or alcohols or other organic solvents. Exemplary solvents include, but are not limited to, acetic acid and acetic acid solutions, ethanol and ethanol solutions, water including acidified water (e.g., having a pH greater than 3 but less than 7), salt solutions, solutions containing free amino acids, sulfate solutions, polyelectrolytes such as polyphosphates or sulfate polysaccharides, complexing agents, and mixtures thereof. In some embodiments, the solvent can include organic solvents such as, for example, alcohols (such as 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 (such as pyrrolidones, for example, polyvinylpyrrolidone (PVP), cyclodextrin) dissolved in a suitable liquid (such as water or an organic liquid).

[0038] Exemplary therapeutic agents that can be delivered with the device 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, polypeptide, polysaccharide, hormone, lipid, interferon, cartilage, recombinant blood cells, synthetic derived blood cells, platelet-rich plasma, cells (autologous or donor cells), melanocytes, stem cells, antimicrobial agents, antibiotics, antibacterial agents, antibodies (including monoclonal antibodies), stem cells, amniotic membrane materials, bovine serum albumin, proteins, coagulation factors, growth factors, cytokines, chemotherapeutics, anti-inflammatory drugs, immunosuppressants, analgesics, blood pressure drugs, antithrombotic agents, anticoagulants, antiplatelet agents, thrombolytic agents, antiproliferative agents, antimitotic agents, inhibitors of restenosis, smooth muscle cell inhibitors, fibrinolytic agents, immunosuppressants, anti-antigen agents, vaccines, and combinations thereof. For example, liquids can include collagen, plasma, chitosan, or a combination thereof.

[0039] refer to Figure 1 and 2 The nebulizer 106 can be any suitable sprayer or atomizer, including, for example, ultrasonic, piezoelectric, pneumatic, mechanical, electrical, vibrating mesh or jet nebulizers. The nebulizer 106 can include an outer chamber 106a, an inner chamber 106b, a needle 107 and a threaded connector 107a. The outer chamber 106a and the inner chamber 106b can be concentric with each other and arranged so that the distal outlet of the outer chamber 106a is communicated with the distal outlet of the inner chamber 106b. The needle 107 can be located radially inward of the outer chamber 106a and the inner chamber 106b, for example, contained in the inner chamber 106b.

[0040] According to some aspects of the present disclosure, fluid reservoir 110 can be arranged relatively close to atomizer. For example, fluid reservoir 110 can be arranged to be less than about 50mm from atomizer 106, for example, from about 1mm to about 50mm. For example, fluid reservoir 110 can be arranged to be less than about 45mm, less than about 40mm, less than about 35mm, less than about 30mm or less than about 25mm from atomizer 106. It is not desirable to be bound by any theory, it is believed that fluid reservoir 110 can be placed relatively close to atomizer 106 to provide effective transmission of fluid. For example, fluid can be supplied to atomizer without injection pump or pipeline or other liquid lines.

[0041] The outer chamber 106a can be connected to a gas source, and the inner chamber 106b can be connected to a fluid source. Figure 2As shown, the gas inlet 108 connects a gas source to the outer chamber 106a of the adapter 120 such that gas is supplied through the gas inlet 108 and enters the outer chamber 106a of the nebulizer 106. Similarly, the fluid inlet 109 connects a fluid source (e.g., fluid reservoir 110) to the inner chamber 106b. As described above, the fluid contained within the fluid reservoir 110 can enter a fluid passage that communicates with the inner chamber 106b of the nebulizer 106. Thus, for example, when the gas flow is turned on, a pressure change within the adapter 120 can draw the fluid from the fluid reservoir 110 into the inner chamber 106b. The gas and fluid then leave the respective distal outlets of the outer chamber 106a and the inner chamber 106b as an aerosol via the nozzle 142 of the distal portion 104 of the adapter 120. The aerosol exiting the nozzle 142 is introduced into the outlet chamber 116 such that the aerosol can be mixed with the plasma that enters the chamber 116 via the plasma outlet 140 adjacent to the nozzle 142 before contacting the surface to be treated with the plasma and the therapeutic agent. The size of the outlet chamber 116 can define a volume sufficient to mix the aerosol with the plasma before deposition onto a surface (such as the tissue of a subject to be treated). The outlet chamber 116 can have various shapes (e.g., conical), where the distal end of the outlet chamber 116 can flare outward 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 the aerosol to be ejected and cover a relatively large surface area to be treated. In some examples, the chamber 116 can narrow at the distal end, for example, to provide a more targeted or focused aerosol and plasma stream onto the surface to be 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. Additionally, for example, the chamber can have a cross-sectional shape with an inner diameter in the range 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.

[0042] In examples of the present disclosure, the outer chamber 106a and the inner chamber 106b can taper towards the needle 107 at or near the nozzle 142. In some examples, the tip of the needle 107 can be flush with the proximal wall of the outlet chamber 116, or the tip can project into the outlet chamber 116. In either case, the tip of the needle 107 can be positioned relative to the nozzle 142 to allow the aerosol to enter the chamber 116.

[0043] Not wishing to be bound by any theory, it is believed that the reduction in the radial cross-section of the outer chamber 106a and the inner chamber 106b can allow for an acceleration of the gas and liquid flow, thereby reducing the pressure. This change in pressure creates a Venturi effect on the inner chamber 106b, where the pressure at the distal outlet of the inner chamber 106b is lower relative to the pressure in the fluid reservoir 110. When the outer chamber 106a is pressurized, the fluid contained in the reservoir 110 is drawn into the inner chamber 106b of the nebulizer 106. The liquid leaving the inner chamber 106b above the tip of the needle 107 can be atomized by the gas leaving the outer chamber 106a through the nozzle 142 to produce an aerosol in the outlet chamber 116.

[0044] In some examples of the present disclosure, the distal end of the outer chamber 106a communicates with the distal end of the inner chamber 106b via an annular opening. For example, the opening can have a uniform annular shape, which can allow gas to flow out of the outer chamber 106a and contact the liquid from the inner chamber 106b, and then flow out through the nozzle 142 into the outlet chamber 116. Adjusting the shape and / or size of the opening (e.g., by adjusting the position of the needle 107) can change the gas flow, thereby changing the shape and / or volume of the resulting spray. For example, a flat hole can produce a fan-shaped spray. In embodiments of the present disclosure, the spray of the atomized fluid has a uniform cone shape. Additionally, reducing the annular distance between the inner diameter of the outer chamber 106a and the outer diameter of the inner chamber 106b can increase the velocity of the gas discharged from the distal end of the outer chamber 106a. The increase in the air flow velocity is expected to further reduce the pressure at the distal end of the inner chamber 106b.

[0045] According to some aspects of the present disclosure, there is a uniform annular opening between the inner chamber 106b and the tip of the needle 107. The size of the annular opening can limit the amount of fluid flowing out of the distal end of the inner chamber 106b. Not wishing to be bound by any theory, the orientation of the distal end of the needle 107 and the corresponding distal ends of the inner chamber 106b and the outer chamber 106a can characterize the aerosol-generating performance of the nozzle 142. The outer chamber 106a can have a nozzle throat, where the nozzle throat corresponds to the smallest diameter portion of the distal end of the outer chamber 106a. The size of the throat relative to the rest of the nozzle 142 and the inlet gas pressure can determine the pressure in the nozzle 142 and thus the intensity of the Venturi effect. The distal end of the inner chamber 106b can be at or near the portion of the nozzle throat of the outer chamber 106a, or outside the nozzle throat of the outer chamber 106a, so that the pressure in the nozzle throat is lower than the pressure in the fluid reservoir 110. Otherwise, the pressure in the nozzle may be higher than the atmospheric pressure (which may prevent the fluid from flowing from the fluid reservoir 110 into the inner chamber 106b), and the gas may flow into the fluid reservoir 110. The distal end of the inner chamber 106b can also be close enough to the distal end of the outer chamber 106a such that the air flow can atomize the liquid. If the distal end of the inner chamber 106b is too far from the distal end of the outer chamber 106a, the liquid may form relatively large droplets.

[0046] The threaded connector 107a of the atomizer 106 can be attached to or integral with the proximal end of the needle 107, where the threaded connector 107a can mate with the internal threads at the proximal portion of the inner chamber 106b. By rotating the threaded connector 107a, the needle 107 can be retracted or advanced, which in turn can increase or decrease the aerosol flow rate from the nozzle 142. The threaded connector 107a can be fixed or adjustable. In an example of the present disclosure, the needle 107 can be advanced and abutted against the inner surface of the distal end of the inner chamber 106b. Further advancing the needle 107 can cause slight deformation of the distal end of the inner chamber 106b such that the distal end is positioned within the distal end of the outer chamber 106a. Retracting the needle 107 creates an annular space between the needle 107 and the distal end of the inner chamber 106b to regulate the fluid path through the nozzle 142 and the generation of aerosol.

[0047] The needle 107 can include any suitable material or combination of materials. Exemplary materials for the needle 107 include, but are not limited to, metals and metal alloys such as stainless steel. The fluid flowing out from the distal end of the inner chamber 106b above the surface of the needle 107 is atomized by the airflow from the distal end of the outer chamber 106a. If the needle 107 is too long (e.g., the needle 107 extends into the chamber 116), some or all of the fluid may flow downward 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 leaving 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 corresponding outer chamber 106a and inner chamber 106b. The shape of the atomizer 106 and / or the nozzle 142 can be configured to provide a desired spray radius and angle formed by the spray. For example, an obtuse angle represents a relatively wide spray radius, while an acute angle represents a relatively small spray radius. In some examples, the distance between the tip of the needle 107 and the distal end of the inner chamber 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.

[0048] The surface of the needle 107 can be smooth enough such that the fluid flows uniformly above the surface to allow for uniform atomization of the fluid. For example, the surface of the needle can be smoothed, for example, by polishing or a similar process. In some examples, the needle 107 can have a surface polished with 800 grit abrasive.

[0049] Figure 3A and 3BA distal perspective view and a proximal perspective view of the outlet chamber 116 are shown, respectively. As shown, the proximal end of the outlet chamber 116 can include a hypotube 132, at least two electrodes 130, and a housing 136 extending in a proximal direction, which surrounds the atomizer 106. The hypotube 132 can be a tubular structure (optionally having a beveled tip) configured to receive a distal tip 182 of the plasma device 180. In some examples, the hypotube 132 is coupled to the chamber 116 by an adhesive (such as a light-cured adhesive). The hypotube 132 can include any suitable material, such as a metal or a metal alloy.

[0050] The hypotube 132 may be in communication with the electrode 130, for example, via a wire. The electrode 130 may be separately housed in, for example, a tube, which may be connected to the proximal side of the outlet chamber 116 by a suitable attachment structure. In some examples, the adapter 120 may include only one electrode 130 or more than two electrodes 130. For example, the adapter 120 may include three or more electrodes 130, for example arranged in a ring. As described above, the hypotube 132 may be connected to each electrode 130 by a conductive material (e.g., a 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, for example, fixed in place by an insulating material (such as a silicone sleeve). The silicone sleeve and the light-curing adhesive may electrically isolate the hypotube 132 and the electrode 130 so as to minimize electrical energy loss at the junction of the respective electrodes 130. The electrode 130 may be housed in a suitable insulating material, such as plastic or silicone.

[0051] In some examples of the present disclosure, the electrode 130 includes a pin that may be flush with the wall of the outlet chamber 116, may be recessed, or may protrude into the outlet chamber 116. In at least one example, the pin of the electrode 130 is recessed or protrudes a distance of about 0.1 mm to about 3 mm, such as about 1 mm to about 2.5 mm, or from about 1.5 mm to about 2.0 mm into the chamber 116. Without wishing to be bound by any theory, it is believed that recessing the pin of the electrode 130 into the chamber 116 may enhance the intensity of the plasma discharge.

[0052] In some examples, the inner cross-sectional area of the hypotube 132 may be substantially equal to the annular outer cross-sectional area between the outer surface of the hypotube 132 and the inner surface of the hypotube 132 passing through the outlet chamber 116. As such, the distance from the hypotube 132 to any point in the gas fluid path may be relatively small, thereby facilitating uniform exposure of the gas to the conductive inner and outer surfaces of the hypotube 132.

[0053] The shape, length, and / or diameter of the exit chamber 116 can be selected based on the desired time that the fluid exiting the nozzle 142 is exposed to the plasma exiting the plasma outlet 140, e.g., to minimize the risk of arcing to a surface (e.g., the tissue of the subject being treated). As described above, for example, the exit chamber 116 can have a generally tubular shape as shown in Figure 1 and 2 . The walls of the exit chamber 116 can flare outward to allow a wider range of ejection of the aerosol and plasma. Without wishing to be bound by any theory, it is believed that the fine atomization of the liquid in a uniform plasma field can promote the uniformity of the interaction between the individual molecules of the plasma and the liquid. The gas source for generating the aerosol can also participate in the energy transfer from the plasma. In some examples, the high-energy arc associated with the plasma can be substantially or completely located within the internal volume defined by the exit chamber 116. Thus, the power exiting the exit chamber 116 may not be sufficient to arc to the tissue of the subject. Bringing the distal end of the exit chamber 116 close to or in contact with the tissue surface can block the flow of the aerosol and plasma and can be used to extinguish the arc at the electrode 130. Referring to Figure 3A and 3B , the electrode 130 can lead to the exit chamber 116 through an opening 140 in the wall of the chamber 116, which defines the plasma outlet 140. As shown in Figure 3B , the opening 140 can be on either side of the nozzle opening 142.

[0054] The features of the adapter 120 can optionally be integrated into the plasma device. Figure 4 An exemplary device 200 in accordance with the present disclosure is shown, including a body 201, a gas tube 208, a fluid reservoir 210, an actuator 212, an exit 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 can provide a power source to generate the plasma. Although Figure 4 shows the gas tube 208 separate from the cable generator 287, in some examples, the cable generator 287 can also provide the gas source.

[0055] The device 200 may include any features of the above-described adapter 120 and / or plasma device 180. For example, similar to the atomizer 106 described above in connection with adapter 120, the atomizer 202 of the illustrated device 200 includes an outer chamber 202a, an inner chamber 202b, a needle 203, and a nozzle 204. The outer chamber 202a may receive gas from a gas tube 208, and the inner chamber 202b may receive fluid from a fluid reservoir 210. Accordingly, the fluid exits the inner chamber 202b at the distal end of the needle 203 to combine with the gas exiting the outer chamber 202a such that the fluid is atomized and enters an outlet chamber 216 as an aerosol through the nozzle 204.

[0056] Figure 4 The fluid reservoir 210 shown therein 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 refilling of the fluid. In other examples, the fluid reservoir 210 may be coupled to the device 200 via complementary mating elements such that the fluid reservoir 210 can be removed from the device 200 to refill or replace the fluid reservoir 210 as needed.

[0057] Once the device 200 is opened via an actuator 212, gas and current may be delivered to the device 200 simultaneously. The gas may create a pressure differential that draws the fluid from the fluid reservoir 210 into the atomizer 201, atomizing the fluid such that the fluid exits the nozzle 204 and enters the outlet chamber 216. The gas may also enter a compartment 206 housing an electrode to create a plasma in the outlet chamber 216. Accordingly, for example, current may be provided to the electrode 207 to create a plasma in the gas entering the outlet chamber 216 via a plasma outlet 205. Figure 4 An exemplary image of a plasma plume is shown.

[0058] Figures 5A - 5E Examples of fluid reservoirs that may be used with the adapter 120, device 200, and any other devices disclosed herein are shown. In some examples, similar to Figure 4 the fluid reservoir 210 shown therein, the fluid reservoir may be integrated into the device.

[0059] Figure 5A and 5B the fluid reservoir shown therein may be in the form of a syringe configured to couple to a fluid inlet of the device. Figure 5A A fluid reservoir 300 having a tapered adapter 310 configured to be received by a fluid inlet 309 of a device is shown. The top 320 of the fluid reservoir may be open or closed. For example, the fluid reservoir may be for single use or may include an open top or an inlet adapted to introduce additional fluid. For example, Figure 5BA fluid reservoir 400 is shown, where the top of the reservoir 400 includes a one-way valve 410. Thus, for example, the fluid reservoir 400 can be filled or refilled with fluid, for example, while avoiding fluid loss. As Figure 5B shown, 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 elements can include threads, luer lock connectors, clips, etc.

[0060] Reference Figure 5C 、 5D and 5E, fluid reservoirs suitable for the devices herein can have various shapes different from syringes, such as vials, bottles, or tubes. Figure 5C A fluid reservoir 500 of is shown in the form of a vial 510, which includes two needles 530, 540 (e.g., double subcutaneous injection needles), which are configured to allow the vial 510 to exhaust air, and supply fluid to the device, for example, via the fluid inlet 570 of the device in communication with the nebulizer. When using the double needles 530, 540, air or other gas under atmospheric pressure can flow into the first needle 530 through the fluid channel 520, and the fluid in the vial 510 can flow out of the reservoir 500 through the second needle 540. The vial 510 can also include a bottle cap 550 and a stopper 560, for example, to prevent liquid spillage. The bottle cap 550 and the stopper 560 can include any suitable material, such as rubber or silicone.

[0061] According to some aspects of the present disclosure, the fluid reservoir can be configured to receive and / or transmit data regarding the fluid reservoir. For example, Figure 5D an exemplary fluid reservoir 600 is shown, which includes a vial 610 (which can be similar to Figure 5C the vial 510 of ) or other suitable container including an electronic chip 620, such as a syringe. The electronic chip can include one or more sensors configured to collect data and measurements and / or a processor that executes various algorithms. The electronic chip 620 can be provided outside the fluid reservoir. For example, as Figure 5D shown, the vial 610 can be coupled to the inside or surface of the fluid reservoir (and can be electrically insulated from the fluid contained in the fluid reservoir), or can be integrated into the wall of the fluid reservoir. The electronic chip 620 can be pre-programmed to identify or measure one or more parameters and / or characteristics of the devices or their components disclosed herein. Exemplary parameters can include dose information (e.g., the amount of the possible dose to be administered per vial), the type of fluid in the vial, the characteristics of the fluid in the vial, such as viscosity, temperature, volume, pH. The fluid reservoir 600 can be electrically coupled to the device and / or a generator / power source used with the device to allow data transmission and / or power the electronic components. In some examples, the electronic chip 620 can be configured to receive and / or send data.

[0062] As Figure 5E The fluid reservoir 700 shown in Figure 5E includes a vial 710 (or other suitable type of container) having mating elements complementary to the mating elements of the fluid inlet 720 of the device. Thus, the fluid reservoir 700 can be selectively coupled to or removed from the device. The fluid inlet 720 of the device can include a fastener defining a surface 740, which can be tapered, for receiving the fluid reservoir 700. The surface 740 defines at least one slot 750 or a plurality of slots 750 that allow the surface 740 to flex to grip the opening of the vial 710.

[0063] Figure 5E Three images are shown: the vial 710 coupled to the fluid inlet 720 of the device, a side view of the fluid inlet 720 with features of the fastener including the surface 740 and the central fluid channel shown by the dashed line, and a top view of the surface 740 including only four slots 750. In some examples, the surface 740 can include only one slot 750, or can include two slots 750, three slots 750, or five or more slots 750, which can be regularly spaced along the surface 740. The fastener can include a flexible or ductile material (such as silicone, rubber, or other flexible polymers), or can include a more rigid or semi-rigid material (e.g., plastic), where the slots 750 provide sufficient clearance or flexibility to allow the tapered surface 740 to accommodate and clamp the vial 710, thereby preventing relative movement between the fluid inlet 720 and the vial 710. In some examples, the vial 710 can include features to facilitate a tight grip. For example, the vial 710 can include a seal 730 to secure the vial 710 within the fluid inlet 720 of the device. The vial 710 can be a single-use vial, or can be configured to be refilled and reused.

[0064] The device herein can be configured for treating external and / or internal tissue. Figure 6A An exemplary catheter system 800 for treating a subject's internal tissue is shown. For example, the system 800 can be used for endoscopic, cystoscopic, and / or laparoscopic procedures. The system 800 shown includes a plasma generator 810, an infusion pump 820, and a catheter 830. The plasma generator 810 can be used to supply gas and / or electricity to the catheter. In some examples, the gas can be supplied to the catheter 830 via a separate gas source independent of the plasma generator 810. The infusion pump 820 can be any suitable infusion system for supplying fluid to the catheter 830. For example, the infusion pump 820 can be manually or automatically operated, e.g., via a user interface that communicates instructions to the electronic components of the infusion pump 820.

[0065] Figure 6BShows an exemplary distal end 900 of a catheter 830, Figure 6C shows Figure 6B end view. As Figure 6B shown, the catheter 820 can accommodate an electrode 910, an atomizer 920, and define an outlet chamber 930 at the distal end 900. The atomizer 920 can include an outer chamber 920a, an inner chamber 920b, and a needle 940, which can be similar to the components of the atomizers 106 and 202 described above in connection with the adapter 120 and the device 200. The electrode 910 can be accommodated in the electrode chamber 912 of the catheter 830. Once the injection pump 820 is activated to allow fluid to flow into the inner chamber 920b of the catheter 830, and the plasma generator 810 is turned on to allow gas to flow into the outer chamber 920a and the electrode chamber 912 and supply power to the electrode chamber 912, current generates plasma and aerosol, which enter the outlet chamber 930. The aerosol exits the atomizer 920 via the nozzle 924, and the plasma exits the electrode chamber 912 via the plasma outlet 926.

[0066] Figure 7A and 7B Another example of the distal end 950 of the catheter 830 of the catheter system 800 is shown. The catheter 830 can include a fluid chamber 970, an electrode 960 accommodated in the electrode chamber 965, and an outlet chamber 990. The gas and electricity supplied to the electrode chamber 965 and the electrode 960 respectively can generate plasma as described above. The plume of plasma can extend at least partially into the outlet chamber 990. The distal end of the fluid chamber 970 is closed by a wall 980, which deflects the fluid and passes it through the narrow orifice of the nozzle 985, generating an aerosol. Thus, the aerosol contacts the plasma and mixes with the energetic species of the plasma within the outlet chamber 990. Figure 7B Shows an end view of the distal end 950 of the catheter 830, including the outlet chamber 990 and the wall 980.

[0067] Figures 6A - 6C The type of catheter system 800 shown in FIGS. 7A - 7B can be used in various medical procedures for treating internal tissues, including, for example, endoscopic, cystoscopic, and / or laparoscopic procedures as described above. In at least one example, the catheter system can be used in tissue removal and / or tissue ablation procedures. For example, after using the catheter system disclosed herein to remove or ablate tissue, a therapeutic agent such as collagen (or any other exemplary therapeutic agent described herein) can be deposited on the surface of the internal tissue. In at least one example, cancerous or pre - cancerous tissue (e.g., cancerous or pre - cancerous tissue of the gastrointestinal tract, such as the esophagus, stomach, intestine, etc.) can be treated with the catheter system disclosed herein.

[0068] Although the principles of the present disclosure are described herein with reference to illustrative aspects of a particular application, the present disclosure is not limited thereto. Those of ordinary skill in the art and those having access to the teachings provided herein will recognize additional modifications, applications, aspects, and substitutions of equivalents that fall within the scope of the aspects described herein. Accordingly, the present disclosure should not be regarded as limited by the foregoing description.

Claims

1. A medical device comprising an adapter, the adapter being configured to be removably coupled to a plasma device, the adapter comprising: A housing, the housing comprising an atomizer, the atomizer comprising: an outer chamber, the outer chamber being in communication with the gas inlet, an inner chamber communicating with the fluid passage and the fluid inlet, and Needle, wherein the needle is located radially inside the inner chamber, the inner chamber is located radially inside the outer chamber, and the distal end of the outer chamber is communicated with the distal end of the inner chamber; at least one electrode; and a chamber defined by a distal portion of the housing, wherein a distally facing surface of the chamber defines at least one plasma outlet and a nozzle in communication with the atomizer; wherein an end of the at least one electrode is proximate to the plasma outlet; and The proximal portion of the chamber includes a hypotube, which is a tubular structure configured to receive an electrode tip of the plasma device when the plasma device is coupled to the adapter so as to electrically connect the electrode tip of the plasma device to the at least one electrode through a conductive material; and to release the electrode tip of the plasma device when the plasma device is detached from the adapter so as to disconnect the electrode tip of the plasma device from the electrical connection with the at least one electrode.

2. The medical device according to 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. The medical device of claim 3, further comprising the plasma device, wherein the adapter is coupled to the plasma device, and wherein the actuator of the housing of the adapter is arranged relative to an actuator of the plasma device to allow a user to control the flow of gas and simultaneously supply power 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 removable from the fluid inlet.

7. The medical device of claim 5, wherein the fluid reservoir contains a liquid comprising 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. The medical device of claim 1, wherein the housing defines a first channel communicating with the outer chamber of the nebulizer and a second channel housing the at least one electrode, a distal end of the second channel defining the plasma outlet.

11. The medical device of claim 1 , wherein the at least one electrode extends through a wall of the chamber.

12. A medical device comprising an adapter, the adapter being configured to be removably coupled to a plasma device, the adapter comprising: A housing, the housing comprising an atomizer, the atomizer comprising: Outer room, Inner room, and Needle, wherein the needle is located radially inside the inner chamber, the inner chamber is located radially inside the outer chamber, and the distal end of the outer chamber is communicated with the distal end of the inner chamber; a fluid reservoir coupled to the fluid inlet, the fluid reservoir containing a fluid including at least one therapeutic agent; at least one electrode; and a chamber defined by a distal portion of the housing, wherein a distally facing surface of the chamber defines at least one plasma outlet and a nozzle in communication with the atomizer; wherein an end of the at least one electrode is proximate to the plasma outlet; and The proximal portion of the chamber includes a hypotube, which is a tubular structure configured to receive an electrode tip of the plasma device when the plasma device is coupled to the adapter so as to electrically connect the electrode tip of the plasma device to the at least one electrode through a conductive material; and to release the electrode tip of the plasma device when the plasma device is detached from the adapter so as to disconnect the electrode tip of the plasma device from the electrical connection with the at least one electrode.

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 removable from the fluid inlet.

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

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

16. The medical device of claim 12, wherein the end of the at least one electrode is recessed from the distal-facing surface of the chamber.

17. The medical device of claim 12, wherein the housing defines a first channel in communication with the outer chamber of the nebulizer and a second channel housing the at least one electrode, 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 an adapter, the adapter being configured to be removably coupled to a plasma device, the adapter comprising: A housing, the housing comprising an atomizer, the atomizer comprising: an outer chamber, the outer chamber being in communication with the gas inlet, an inner chamber communicating with the fluid inlet, and Needle, wherein the needle is located radially inwardly of each of the inner chamber and the outer chamber, and a distal end of the outer chamber is in communication with a distal end of the inner chamber; at least one electrode; a fluid reservoir coupled to the fluid inlet; and a chamber defined by a distal portion of the housing, wherein a distally facing surface of the chamber defines at least one plasma outlet and a nozzle in communication with the atomizer; wherein an end of the at least one electrode is proximate to the plasma outlet; and The proximal portion of the chamber includes a hypotube, which is a tubular structure configured to receive an electrode tip of the plasma device when the plasma device is coupled to the adapter so as to electrically connect the electrode tip of the plasma device to the at least one electrode through a conductive material; and to release the electrode tip of the plasma device when the plasma device is detached from the adapter so as to disconnect the electrode tip of the plasma device from the electrical connection with the at least one electrode.

Images