Methods and apparatus for modifying or killing cells by manipulating the cell membrane charging time

1 . A method of treatment comprising modifying and/or killing a cell by changing a cell membrane charging time to make the cell more susceptible to an influence of an electric field,

wherein changing the cell membrane charging time comprises:

inserting one or more electrodes into or adjacent to tissue surrounding the cell;

acquiring a temperature of the tissue;

delivering, via the one or more electrodes, electrical energy to the tissue by a plurality of electrical pulses; and

increasing the temperature of the tissue using the electrical energy delivered to the tissue, to thereby change the cell membrane charging time,

wherein increasing the temperature of the tissue comprises dynamically controlling a rate of energy delivery of the electrical energy such that the temperature of the tissue rises above a first critical temperature and remains below a second critical temperature.

2 . The method of claim 1 , wherein changing the cell membrane charging time further comprises changing a response of a transmembrane potential due to the electrical pulses.

3 . The method of claim 1 , wherein modifying the cell comprises modifying a genome and/or a gene expression of the cell.

4 . The method of claim 1 , wherein modifying the cell comprises making it easier for drugs, nucleic acids, and/or molecules to cross the cell membrane.

5 . The method of claim 1 , wherein modifying the cell comprises making the cell a target of an immune system of a host of the cell.

6 . The method of claim 1 , wherein dynamically controlling the rate of energy delivery of the electrical energy such that the temperature of the tissue rises above the first critical temperature and remains below the second critical temperature comprises adjusting at least one of a time delay between ones of the electrical pulses, a width of one or more of the electrical pulses, or an amplitude of one or more of the electrical pulses.

7 . The method of claim 1 , wherein the temperature of the tissue is increased by at least 5° C. using the electrical energy.

8 . The method of claim 1 , wherein the rate of energy delivery of the electrical energy is dynamically controlled to increase the temperature of the tissue above the first critical temperature and to maintain the temperature of the tissue at a value between the first and second critical temperatures until an end of delivery of the electrical energy.

9 . The method of claim 1 , wherein the first critical temperature is between 37° C. and 55° C., and

wherein the second critical temperature is between 45° C. and 95° C.

10 . The method of claim 1 , wherein dynamically controlling the rate of energy delivery of the electrical energy such that the temperature of the tissue rises above the first critical temperature and remains below the second critical temperature comprises adjusting a duty cycle of the electrical pulses.

11 . The method of claim 1 , wherein dynamically controlling the rate of energy delivery of the electrical energy such that the temperature of the tissue rises above the first critical temperature and remains below the second critical temperature comprises adjusting a width of at least one of the electrical pulses.

12 . The method of claim 1 , wherein one or more of the electrical pulses are between 250 V and 10,000 V in amplitude.

13 . The method of claim 1 , wherein the electrical pulses comprise a positive polarity electrical pulse, followed by a first time delay, then a negative polarity pulse followed by a second time delay.

14 . The method of claim 13 , wherein the first time delay is equal to the second time delay and is between 100 ns and 100 μs in duration.

15 . The method of claim 13 , wherein the first time delay is shorter than the second time delay, and

wherein the first time delay is between 10 ns and 100 μs in duration, and the second time delay is between 10 μs and 10 seconds in duration.

16 . The method of claim 13 , wherein the first time delay is predetermined, and

wherein the second time delay is selected based on the temperature of the tissue.

17 . The method of claim 1 , further comprising delivering the electrical energy until a specific dose is achieved,

wherein the specific dose is calculated as a total number of the electrical pulses delivered, and

wherein the total number of the electrical pulses delivered is between 100 and 100,000 pulses.

18 . The method of claim 1 , wherein dynamically controlling the rate of energy delivery of the electrical energy such that the temperature of the tissue rises above the first critical temperature and remains below the second critical temperature comprises sequentially increasing widths of at least two consecutive electrical pulses among the plurality of electrical pulses.

19 . An apparatus for preventing, mitigating, and/or reducing tissue damage during a pulsed electric field therapy comprising a plurality of electrical pulses, the apparatus comprising circuitry configured to modify and/or kill a cell by changing a cell membrane charging time to make the cell more susceptible to an influence of an electric field,

wherein the apparatus comprises:

one or more electrodes configured to deliver electrical energy, via the electrical pulses, to tissue surrounding the cell; and

one or more temperature sensors configured to acquire a temperature of the tissue,

wherein the apparatus is configured to increase the temperature of the tissue using the electrical energy delivered to the tissue, to thereby change the cell membrane charging time, and

wherein the apparatus is configured to dynamically control a rate of energy delivery of the electrical energy such that the temperature of the tissue rises above a first critical temperature and remains below a second critical temperature.

20 . A method of treatment comprising modifying and/or killing a cell by changing a cell membrane charging time to make the cell more susceptible to an influence of an electric field,

wherein changing the cell membrane charging time comprises:

inserting one or more electrodes into or adjacent to tissue surrounding the cell;

delivering, via the one or more electrodes, electrical energy to the tissue by a plurality of electrical pulses; and

increasing a temperature of the tissue using the electrical energy delivered to the tissue, to thereby change the cell membrane charging time,

wherein a width of at least one of the electrical pulses is less than or equal to the cell membrane charging time.