# US 11,298,175 B2 · Asymmetric balanced waveform for AC cardiac irreversible electroporation

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- Number: US 11,298,175 B2
- Document ID: US11298175B2
- Status: Granted
- Kind: B2
- Application number: 15/152,873
- Filed: 2016-05-12
- Published: 2016-11-17
- Granted: 2022-04-12
- Earliest claimed: 2015-05-12
- Assignees: St. Jude Medical, Atrial Fibrillation Division, Inc.
- Applicants: UMC Utrecht Holding B. V.
- Inventors: Maurits K. Konings
- Web page: https://patentgrep.com/patent/US11298175B2

## CPC

- A61B 18/1206: {Generators therefor}
- A61B 18/1492: {having a flexible, catheter-like structure, e.g. for heart ablation (A61B18/1477 takes precedence)}
- A61N 1/327: {for enhancing the absorption properties of tissue, e.g. by electroporation}
- A61B 2018/00351: {Heart}
- A61B 2018/00577: {Ablation}
- A61B 2018/00613: {Irreversible electroporation}
- A61B 2018/00642: {with feedback, i.e. closed loop control}
- A61B 2018/00839: {Bioelectrical parameters, e.g. ECG, EEG}
- A61B 2018/1266: {with DC current output}
- 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)

## Abstract

An electroporation therapy apparatus method, and system is provided. The apparatus, system, and method comprise an electroporation generator (26). The electroporation generator (26) is configured to output an asymmetric balanced waveform to a medical device, and the asymmetric balanced waveform comprises a first positive phase and a first negative phase. The first positive phase comprises a first current and a first time and the first negative phase comprises a second current and a second time. The first current is greater than the second current and the second time is greater than the first time. The asymmetric balanced waveform is configured to irreversibly electroporate a target tissue.

## Claims

### Claim 1

An electroporation therapy apparatus, comprising:
an electroporation generator, wherein the electroporation generator is configured to output an asymmetric balanced waveform to a medical device comprising an electrode assembly having a plurality of electrode elements, wherein the electroporation generator is further configured to receive a signal for identifying which pairs of the plurality of electrode elements have electrical characteristics indicative of contact with a target tissue when the target tissue is energized with an excitation signal, and wherein the electroporation generator is configured to use an electroporation energization strategy to energize at least one of the pairs of the plurality of electrode elements identified as having contact with the target tissue with the asymmetric balanced waveform,
wherein the asymmetric balanced waveform comprises a first positive phase and a first negative phase, wherein the first positive phase comprises a first current and a first time and wherein the first negative phase comprises a second current and a second time,
wherein the first current is greater than the second current and wherein the second time is greater than the first time, and
wherein the asymmetric balanced waveform is configured to irreversibly electroporate the target tissue non-linearly as a function of a variable current density imposed on the target tissue from the first and second currents over the first and second times to enhance the irreversible electroporation, and wherein the asymmetric balanced waveform is further configured to provide a production rate of new pores that is enhanced in a non-linear manner when a time duration of a transmembrane voltage is reduced by a factor 2 and an amplitude of the transmembrane voltage is multiplied by a factor 2.

### Claim 2 (depends on 1)

The electroporation therapy apparatus of claim 1, wherein the first positive phase and the first negative phase comprises a cycle and wherein the electroporation generator is configured to output a plurality of cycles to the target tissue.

### Claim 3 (depends on 2)

The electroporation therapy apparatus of claim 2, wherein the electroporation generator is configured to insert a latency period between the first positive phase and the first negative phase and between each of the plurality of cycles.

### Claim 4 (depends on 3)

The electroporation therapy apparatus of claim 3, wherein the latency period between each of the plurality of cycles is less than 0.5 seconds.

### Claim 5 (depends on 2)

The electroporation therapy apparatus of claim 2, wherein combined area of each positive phase and each negative phase in each of the plurality of cycles is near zero.

### Claim 6 (depends on 2)

The electroporation therapy apparatus of claim 2, wherein the plurality of cycles is configured to apply an applied current function to the target tissue.

### Claim 7 (depends on 6)

The electroporation therapy apparatus of claim 6, wherein the applied current function comprises a value of 0.5 Volts.

### Claim 8 (depends on 1)

The electroporation therapy apparatus of claim 1, wherein the electroporation generator is further configured to receive a signal indicative of a tissue state.

### Claim 9 (depends on 8)

The electroporation therapy apparatus of claim 8, wherein the electroporation generator is further configured to calculate and set the asymmetric balanced waveform using the received signal.

### Claim 10 (depends on 9)

The electroporation therapy apparatus of claim 9, wherein the electroporation generator is configured to calculate the asymmetric balanced waveform to minimize a neurostimulation of the target tissue.

### Claim 11 (depends on 1)

The method of claim 1, wherein the electroporation generator is configured to determine whether neurostimulation will occur using the equation
∀
t
⁢
⁢
ϵ
⁡
[
0
,
τ
chron
]
⁢
:
⁢
⁢
∫
0
t
⁢
E
m
⁢
⁢
d
⁢
⁢
τ
=
∫
0
t
⁢
1
a
m
⁢
⁢
Φ
m
⁢
d
⁢
⁢
τ
<
S
threshold
,
in which τchron is chronaxie time, Em is an applied electrical field over a membrane of the target tissue, am is a thickness of the membrane, Φm is n voltage over the membrane, and Sthreshold is stimulation threshold.

### Claim 12

A method of applying irreversible electroporation to a target tissue, comprising:
sending an asymmetric balanced waveform from an electroporation generator to a medical device comprising an electrode assembly having a plurality of electrode elements, wherein the electroporation generator is configured to receive a signal for identifying which pairs of the plurality of electrode elements have electrical characteristics indicative of contact with the target tissue when the target tissue is energized with an excitation signal, and wherein the electroporation generator is configured and to use an electroporation energization strategy to energize at least one of the pairs of the plurality of electrode elements identified as having contact with the target tissue with the asymmetric balanced waveform,
wherein the asymmetric balanced waveform comprises a first positive phase and a first negative phase, wherein the first positive phase comprises a first current and a first time and wherein the first negative phase comprises a second current and a second time,
wherein the first current is greater than the second current and wherein the second time is greater than the first time, and
wherein the asymmetric balanced waveform is configured to enhance electroporation in a non-linear manner while also minimizing neurostimulation of the target tissue, and wherein the asymmetric balanced waveform is further configured to provide a production rate of new pores that is enhanced in a non-linear manner when a time duration of a transmembrane voltage is reduced by a factor 2 and an amplitude of the transmembrane voltage is multiplied by a factor 2.

### Claim 13 (depends on 12)

The method of claim 12, wherein the first positive phase and the first negative phase comprises a cycle and wherein the electroporation generator is configured to output a plurality of cycles to the target tissue.

### Claim 14 (depends on 13)

The method of claim 13, wherein the electroporation generator is configured to insert a latency period between the first positive phase and the first negative phase and between each of the plurality of cycles.

### Claim 15 (depends on 14)

The method of claim 14, wherein the latency period between each of the plurality of cycles is less than 0.5 seconds.

### Claim 16 (depends on 13)

The method of claim 13, wherein a combined area of each positive phase and each negative phase in each of the plurality of cycles is near zero.

### Claim 17 (depends on 13)

The method of claim 13, wherein the plurality of cycles is configured to apply an applied current function to the target tissue.

### Claim 18 (depends on 12)

The method of claim 12, wherein the electroporation generator is configured to calculate the asymmetric balanced waveform to minimize a neurostimulation of the target tissue.

### Claim 19 (depends on 12)

The method of claim 12, wherein the electroporation generator is configured to determine whether neurostimulation will occur using the equation
∀
t
⁢
⁢
ϵ
⁡
[
0
,
τ
chron
]
⁢
:
⁢
⁢
∫
0
t
⁢
E
m
⁢
⁢
d
⁢
⁢
τ
=
∫
0
t
⁢
1
a
m
⁢
⁢
Φ
m
⁢
d
⁢
⁢
τ
<
S
threshold
,
in which τchron is chronaxie time, Em is an applied electrical field over a membrane of the target tissue, am is a thickness of the membrane, Φm is n voltage over the membrane, and Sthreshold is stimulation threshold.

### Claim 20

An electroporation therapy system, comprising:
a medical device comprising a plurality of electrode elements; and
an electroporation generator, wherein the electroporation generator is configured to output an asymmetric balanced waveform to the plurality of electrode elements, and wherein the electroporation generator is further configured to receive a signal for identifying which pairs of the plurality of electrode elements have electrical characteristics indicative of contact with a target tissue when the target tissue is energized with an excitation signal, and wherein the electroporation generator is configured to use an electroporation energization strategy to energize at least one of the pairs of the plurality of electrode elements identified as having contact with the target tissue with the asymmetric balanced waveform,
wherein the asymmetric balanced waveform comprises a first positive phase and a first negative phase, wherein the first positive phase comprises a first current and a first time and wherein the first negative phase comprises a second current and a second time,
wherein the first current is greater than the second current and wherein the second time is greater than the first time, and
wherein the asymmetric balanced waveform configured to irreversibly electroporate the target tissue, and wherein the electroporation generator is configured to determine whether neurostimulation will occur using the equation
∀
t
⁢
⁢
ϵ
⁡
[
0
,
τ
chron
]
⁢
:
⁢
⁢
∫
0
t
⁢
E
m
⁢
⁢
d
⁢
⁢
τ
=
∫
0
t
⁢
1
a
m
⁢
⁢
Φ
m
⁢
d
⁢
⁢
τ
<
S
threshold
,
in which τchron is chronaxie time, Em is an applied electrical field over a membrane of the target tissue, am is a thickness of the membrane, Φm is a voltage over the membrane, and Sthreshold is stimulation threshold.