Systems and methods for improved tissue-sensing based electroporation

Abstract

An adaptive control method for controlling EP pulse parameters during electroporation (EP) of cells or tissue using an EP system includes providing a system for adaptive control to optimize EP pulse parameters including EP pulse parameters, applying voltage and current excitation signals to the cells, obtaining data from the current and voltage measurements, and processing the data to separate the desirable data from the undesirable data, extracting relevant features from the desirable data, applying at least a portion of the relevant features to a trained diagnostic model, estimating EP pulsing parameters based on an outcome of the applied relevant features, where the initialized EP pulsing parameters are based on the trained model and the relevant features, to optimize the EP pulsing parameters, and applying, by the generator, a first EP pulse based on the first pulsing parameters.

1 .- 20  (canceled) 
     
     
         21 . An electroporation (EP) system comprising:
 at least two electroporation electrodes (EPEs) configured to be positioned in or adjacent to a tissue;   a signal generator electrically connected to the at least two EPEs and generating at least one electrical signal based on at least one control parameter, wherein the at least one electrical signal is applied to the tissue via the at least two EPEs;   a measurement device electrically connected to the at least two EPEs and generating measured sensor data; and   a controller configured to:
 receive the measured sensor data from the measurement device, and 
 update the at least one control parameter based at least in part on the measured sensor data. 
   
     
     
         22 . The EP system of  claim 21 , wherein the at least one electrical signal comprises at least one of an excitation signal or an electroporation pulse. 
     
     
         23 . The EP system of  claim 21 , wherein the measurement device comprises a voltage sensor, wherein the measured sensor data indicates a measured voltage across the tissue when the at least one electrical signal is applied. 
     
     
         24 . The EP system of  claim 21 , wherein the measurement device comprises a current sensor, wherein the measured sensor data indicates a measured current across the tissue when the at least one electrical signal is applied. 
     
     
         25 . The EP system of  claim 21 , wherein the at least one control parameter comprises a time constant for a pulse width of the at least one electrical signal to be applied to the tissue. 
     
     
         26 . The EP system of  claim 21 , further comprising:
 at least one probe configured to receive one or more therapeutic moieties and deliver the one or more therapeutic moieties to the tissue.   
     
     
         27 . The EP system of  claim 26 , wherein the controller determines whether the one or more therapeutic moieties are present at or adjacent to the at least two EPEs based on a plurality of resistance or impedance measurements from the measured sensor data. 
     
     
         28 . The EP system of  claim 27 , wherein the controller is configured to detect a presence of the one or more therapeutic moieties in an instance in which a decrease in resistance or impedance is detected based on the plurality of resistance or impedance measurements. 
     
     
         29 . The EP system of  claim 26 , wherein the one or more therapeutic moieties comprise plasmid DNA. 
     
     
         30 . The EP system of  claim 21 , wherein the controller is configured to apply the measured sensor data to at least one trained diagnostics model. 
     
     
         31 . A method comprising:
 generating, by a signal generator of an electroporation (EP) system, at least one electrical signal based at last in part on at least one control parameter;   applying, by at least two electroporation electrodes (EPEs) of the EP system, the at least one electrical signal to a tissue;   receiving, by a controller of the EP system, measured sensor data from a measurement device electrically connected to the at least two EPEs; and   updating, by the controller, the at least one control parameter based at least in part on the measured sensor data.   
     
     
         32 . The method of  claim 31 , wherein the at least one electrical signal comprises at least one of an excitation signal or an electroporation pulse. 
     
     
         33 . The method of  claim 31 , wherein the measured sensor data indicates a measured voltage across the tissue in response to the at least one electrical signal. 
     
     
         34 . The method of  claim 31 , wherein the measured sensor data indicates a measured current across the tissue in response the at least one electrical signal. 
     
     
         35 . The method of  claim 31 , wherein the at least one control parameter comprises a time constant for a pulse width of the at least one electrical signal to be applied to the tissue. 
     
     
         36 . The method of  claim 31  further comprising:
 delivering, by at least one probe of the EP system, one or more therapeutic moieties to the tissue. 
 
     
     
         37 . The method of  claim 36 , further comprising:
 determining whether the one or more therapeutic moieties are present at or adjacent to the at least two EPEs based on a plurality of resistance or impedance measurements from the measured sensor data.   
     
     
         38 . The method of  claim 37 , further comprising:
 determining a presence of the one or more therapeutic moieties in response to detecting a decrease in resistance or impedance based on the plurality of resistance or impedance measurements.   
     
     
         39 . The method of  claim 36 , wherein the one or more therapeutic moieties comprise plasmid DNA. 
     
     
         40 . The method of  claim 31 , further comprising:
 applying, by the controller, the measured sensor data to at least one trained diagnostics model.