# US 12,006,507 B2 · Electroporation with active compensation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,006,507 B2 - Document ID: US12006507B2 - Status: Granted - Kind: B2 - Application number: 16/935,987 - Filed: 2020-07-22 - Published: 2022-01-27 - Granted: 2024-06-11 - Earliest claimed: 2020-07-22 - Assignees: NantCell, Inc. - Applicants: NantCell, Inc. - Inventors: Chih-Wei Chang; Jon Thomas Van Lew; Artin Mehrabi - Web page: https://patentgrep.com/patent/US12006507B2 ## CPC - C12N 15/87: Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation - A61N 1/08: Arrangements or circuits for monitoring, protecting, controlling or indicating {(for external stimulators A61N1/3603; for implantable neurostimulators A61N1/36128; for heart stimulators A61N1/37; for defibrillators A61N1/3925)} - C12M 35/02: {Electrical or electromagnetic means, e.g. for electroporation or for cell fusion} - C12M 41/48: {Automatic or computerized control (automatic analysis G01N35/00)} - A61N 1/0476: {Array electrodes (including any electrode arrangement with more than one electrode for at least one of the polarities)} - A61N 1/378: Electrical supply - H03K 3/00: Circuits for generating electric pulses; Monostable, bistable or multistable circuits (H03K4/00 takes precedence; for digital function generators in computers G06F1/02) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - 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) - C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS} - H03K: PULSE TECHNIQUE (measuring pulse characteristics G01R; modulating sinusoidal oscillations with pulses H03C; transmission of digital information H04L; discriminator circuits detecting phase difference between two signals by counting or integrating cycles of oscillation H03D3/04; automatic control, starting, synchronisation or stabilisation of generators of electronic oscillations or pulses where the type of generator is irrelevant or unspecified H03L; coding, decoding or code conversion, in general H03M) ## Abstract An apparatus for electroporating cells with a cargo includes electrodes defining a path for a fluid including the cells and the cargo to flow, a power source coupled across the electrodes, and a control circuit. In some examples, the control circuit is configured to detect a decrease in an induced current due to an increase in a resistance between the electrodes, and control the power source to increase the induced current to maintain an electric field between the electrodes. A future value of the resistance between the electrodes may be predicted based on previous values of the resistance. In other examples, the control circuit is configured to detect parameters of the fluid flowing between the electrodes, and control the power source to generate or stop generating electrical pulses in response to detecting the parameters. Other example apparatuses, and methods of electroporating cells with a cargo is also disclosed. ## Claims ### Claim 1 An apparatus for electroporating cells with a cargo, the apparatus comprising: two electrodes spaced apart from each other and defining a path for a fluid including the cells and the cargo to flow therebetween, the electrodes having a resistance therebetween when fluid flows through the path; a DC power source coupled across the electrodes; and a control circuit configured to control the DC power source to provide a plurality of electrical pulses at a voltage to the electrodes to induce a current through the electrodes for generating an electric field between the electrodes at a defined value, detect a decrease in the induced current due to an increase in the resistance between the electrodes, determine at least a first value and a second value of the resistance between the electrodes over a period of time, apply a linear projection between the first value of the resistance and the second value of the resistance, predict a future value of the resistance between the electrodes based on the linear projection, and control the DC power source to increase the induced current based on the future value of the resistance to maintain the electric field between the electrodes at the defined value. ### Claim 2 (depends on 1) The apparatus of claim 1, wherein the control circuit is configured to apply the linear projection based on a data length of a defined number of electrical pulses. ### Claim 3 (depends on 1) The apparatus of claim 1, wherein the control circuit is configured to determine the first value of the resistance when the induced current is at a defined value. ### Claim 4 (depends on 3) The apparatus of claim 3, wherein the defined value of the induced current is a peak value of the induced current. ### Claim 5 (depends on 1) The apparatus of claim 1, wherein the control circuit is configured to control the DC power source to increase the induced current to a defined value. ### Claim 6 (depends on 5) The apparatus of claim 5, wherein the defined value of the induced current is a peak value of the induced current. ### Claim 7 (depends on 1) The apparatus of claim 1, wherein the control circuit is configured to control the DC power source to increase the voltage of the plurality of electrical pulses to increase the induced current. ### Claim 8 (depends on 1) The apparatus of claim 1, wherein the control circuit includes at least one of a proportional-integral-derivative controller, a proportional-integral controller, a proportional-derivative controller, and a proportional controller. ### Claim 9 (depends on 8) The apparatus of claim 8, wherein a gain factor of the at least one of the proportional-integral-derivative controller, the proportional-integral controller, the proportional-derivative controller, and/or the proportional controller is fixed or variable. ### Claim 10 (depends on 1) The apparatus of claim 1, wherein the control circuit is configured to detect a parameter associated with the fluid, and in response to detecting the parameter associated with the fluid, control the DC power source to generate the plurality of electrical pulses. ### Claim 11 (depends on 10) The apparatus of claim 10, wherein the parameter associated with the fluid is a first parameter, and wherein the control circuit is configured to detect a second parameter associated with the fluid, and in response to detecting the second parameter associated with the fluid, control the DC power source to stop generating the plurality of electrical pulses. ### Claim 12 A method of electroporating cells with a cargo, the method comprising: flowing a fluid including the cells and the cargo in a path defined by two electrodes spaced apart from each other, the electrodes having a resistance therebetween when fluid flows through the path; controlling a DC power source to provide a plurality of electrical pulses at a voltage to the electrodes to induce a current through the electrodes to generate an electric field between the electrodes at a defined value; detecting a decrease in the induced current due to an increase in the resistance between the electrodes; determining at least a first value and a second value of the resistance between the electrodes over a period of time; applying a linear projection between the first value of the resistance and the second value of the resistance; predicting a future value of the resistance between the electrodes based on the linear projection; and controlling the DC power source to increase the induced current based on the future value of the resistance to maintain the electric field between the electrodes at the defined value. ### Claim 13 (depends on 12) The method of claim 12, wherein applying the linear projection between the first value of the resistance and the second value of the resistance includes applying the linear projection based on a data length of a defined number of electrical pulses. ### Claim 14 (depends on 12) The method of claim 12, wherein determining the first value of the resistance includes determining the first value of the resistance when the induced current is at a defined value. ### Claim 15 (depends on 14) The method of claim 14, wherein the defined value of the induced current is a peak value of the induced current. ### Claim 16 (depends on 12) The method of claim 12, wherein controlling the DC power source includes controlling the DC power source to increase the induced current to a defined value. ### Claim 17 (depends on 16) The method of claim 16, wherein the defined value of the induced current is a peak value of the induced current. ### Claim 18 (depends on 12) The method of claim 12, wherein controlling the DC power source includes controlling the DC power source to increase the voltage of the plurality of electrical pulses to increase the induced current.