# US 11,304,750 B2 · Low-temperature plasma catheter for less-invasive, localized treatment of endocarditis and atherosclerosis

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- Number: US 11,304,750 B2
- Document ID: US11304750B2
- Status: Granted
- Kind: B2
- Application number: 16/637,168
- Filed: 2018-08-09
- Published: 2020-07-23
- Granted: 2022-04-19
- Earliest claimed: 2017-08-09
- Assignees: The Penn State Research Foundation
- Applicants: The Penn State Research Foundation
- Inventors: Sean David Knecht; Christopher A. Siedlecki; Sven Gunnar Bilen; Michael Matthew Micci; Ian Gilchrist; Girish Soorappa Kirimanjeswara
- Web page: https://patentgrep.com/patent/US11304750B2

## CPC

- A61B 18/00: Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body (eye surgery A61F9/007; ear surgery A61F11/00)
- A61B 18/1492: {having a flexible, catheter-like structure, e.g. for heart ablation (A61B18/1477 takes precedence)}
- A61N 1/44: Applying ionised fluids {(ion generators H01J37/00)}
- A61B 2018/00083: {low, i.e. electrically insulating}
- A61B 2018/00357: {Endocardium}
- A61B 2018/0041: {Removal of thrombosis}
- A61B 2018/00583: {Coblation, i.e. ablation using a cold plasma}
- A61B 2018/00714: {Temperature}
- A61B 2018/00982: {combined with or comprising means for visual or photographic inspections inside the body, e.g. endoscopes}
- A61B 2018/0212: {using an instrument inserted into a body lumen, e.g. catheter}
- A61B 2018/046: {in liquid form}
- A61B 2018/122: {ionizing, with corona}
- A61B 2018/147: {Electrodes transferring energy by capacitive coupling, i.e. with a dielectricum between electrode and target tissue}
- A61B 2018/1475: {Electrodes retractable in or deployable from a housing}
- H05H 2245/30: Medical applications
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- H05H: PLASMA TECHNIQUE (apparatus or processes specially adapted for producing X-rays H05G2/00); PRODUCTION OF ACCELERATED ELECTRICALLY-CHARGED PARTICLES OR OF NEUTRONS; PRODUCTION OR ACCELERATION OF NEUTRAL MOLECULAR OR ATOMIC BEAMS

## Abstract

Various aspects of the invention relate to methods and devices for treating diseases and conditions including atherosclerosis and endocarditis using low-temperature, non-equilibrium plasmas. A device may be, for example, a catheter that carries electrodes and a dielectric material for generating a localized, non-equilibrium plasma in a bodily fluid such as blood.

## Claims

### Claim 1

A method of treating a disease or condition in a subject, the method comprising:
contacting the subject with a catheter comprising a lumen carrying a first electrode and a second electrode spaced apart from the first electrode by a dielectric;
causing the first electrode, the second electrode and/or the dielectric to contact with a bodily fluid of the subject; and
providing an electric current via the first electrode or the second electrode, thereby producing a localized, non-equilibrium plasma from the bodily fluid of the subject,
wherein less than 1 mL of a gas is generated in the subject after providing the electric current and producing the localized, non-equilibrium plasma from the bodily fluid.

### Claim 2 (depends on 1)

The method of claim 1, wherein the disease or condition is atherosclerosis or endocarditis.

### Claim 3 (depends on 1)

The method of claim 1, wherein:
the localized, non-equilibrium plasma ablates either a structure associated with the disease or condition or a portion of the structure;
the localized, non-equilibrium plasma generates a reactive molecule or ion, and the reactive molecule or ion ablates either a structure associated with the disease or condition or a portion of the structure; or
the localized, non-equilibrium plasma generates a therapeutic molecule, wherein the therapeutic molecule is toxic to a pathogen, the therapeutic molecule initiating intracellular signaling, or the therapeutic molecule has a physiological effect.

### Claim 4 (depends on 1)

The method of claim 1, wherein:
the localized, non-equilibrium plasma generates a reactive molecule or ion;
the reactive molecule or ion ablates either a structure associated with the disease or condition or a portion of the structure; and
the reactive molecule or ion is a reactive oxygen species (ROS) or a reactive nitrogen species (RNS).

### Claim 5 (depends on 4)

The method of claim 4, wherein the ROS or RNS is selected from H2O2 (hydrogen peroxide), .OH (hydroxyl radical), O2.- (superoxide anion radical), O3 (ozone), .O2 (singlet oxygen), O (monomeric oxygen), NO2- (nitrite), NO3- (nitrate), nitric oxide (NO), and ONOO— (peroxynitrite).

### Claim 6 (depends on 4)

The method of claim 4, wherein the structure comprises atheromatous plaque, fibroatheroma, arterial fibrosis, low-density lipoprotein (LDL) particles, a thrombus, fibrin, a calcium deposit, a tumor, malignant cells, cancerous cells, sarcoma, a virus, a parasite, a bacterium, or a bacterial biofilm.

### Claim 7 (depends on 1)

The method of claim 1, wherein a temperature of the bodily fluid increases by more than 5° C. for a period of time less than 1 minute after the localized, non-equilibrium plasma is produced.

### Claim 8 (depends on 1)

The method of claim 1, wherein producing the localized, non-equilibrium plasma does not generate an air embolism in the subject.

### Claim 9 (depends on 1)

The method of claim 1, wherein the localized, non-equilibrium plasma comprises a series of localized, non-equilibrium plasmas with a repetition rate of 0.1 Hz to 20 kHz and a pulse-width of 10 ns to 1 μs.

### Claim 10 (depends on 1)

The method of claim 1, wherein providing the electric current comprises providing the electric current at an operating-voltage of 1 kV to 30 kV.

### Claim 11 (depends on 1)

The method of claim 1, wherein the non-equilibrium plasma has one or more of:
an electron density greater than 1022 electrons per cubic meter;
a power density greater than 1012 watts per cubic meter; and
an electric field greater than 100 kV per cm.

### Claim 12 (depends on 1)

The method of claim 1, wherein the localized, non-equilibrium plasma generates a local increase in pressure and/or the non-equilibrium plasma generates a shockwave in the bodily fluid.

### Claim 13 (depends on 1)

The method of claim 1, wherein providing the electric current causes a spark discharge, a streamer discharge, or a corona discharge.

### Claim 14 (depends on 1)

The method of claim 1, wherein causing the first electrode, the second electrode, and/or the dielectric to contact the bodily fluid further comprises causing the first electrode, the second electrode, and/or the dielectric to exit the lumen of the catheter via an aperture of the lumen and come into contact with the bodily fluid.

### Claim 15

A method of treating a disease or condition in a subject, the method comprising:
contacting the subject with a catheter comprising a distal aperture fluidly coupled to a lumen carrying a first electrode and a second electrode spaced apart from the first electrode by a dielectric;
expelling the first electrode, the second electrode, and/or the dielectric from the lumen of the catheter through the distal aperture of the catheter into contact with a bodily fluid of the subject;
providing an electric current via the first electrode or the second electrode, thereby producing a localized, non-equilibrium plasma from the bodily fluid of the subject,
wherein less than 1 mL of a gas is generated in the subject after providing the electric current and producing the localized, non-equilibrium plasma from the bodily fluid; and
retracting the one or more of the first electrode, the second electrode, and the dielectric into the lumen of the catheter through the distal aperture of the catheter.

### Claim 16 (depends on 15)

The method of claim 15, wherein providing the electric current comprises providing the electric current at an operating-voltage of 1 kV to 30 kV.