High voltage nanosecond pulse generator using fast recovery diodes for cell electro-manipulation

• US 7,767,433 B2
• Filed: 04/13/2006
• Issued: 08/03/2010
• Est. Priority Date: 04/22/2005
• Status: Active Grant

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Gundersen, Martin A., Kuthi, Andras
• Primary Examiner(s): Beisner; William H
• Assistant Examiner(s): Hobbs; Michael
• Application Number:
  US11/279,697
• Publication Number:
  US 20070031959A1
• Time in Patent Office: 1,573 Days
• Field of Search: 435/173.6, 435/285.2, 435/461
• US Class Current: 435/285.2
• CPC Class Codes: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
• CPC Class Codes: H03K 17/74 by the use, as active elements, of diodes by the use of more than one type of semiconductor device H03K17/567; by the use of tunnel diodes H03K17/58; by the use of negative resistance diodes H03K17/70
• CPC Class Codes: H03K 3/57 the switching device being a semiconductor device
• CPC Class Codes: H03K 5/12 by steepening leading or trailing edges

Abstract

A pulse generator circuit may include a diode configured to operate as an opening switch, a tank circuit in series with the diode having an admittance that is switchable from a first value to a second value that is different from the first value, and a switching system configured to cause the tank circuit to switch between the first value and the second value. The diode may saturate in less than 100 nanoseconds. A saturable core transformer may operate as a switch that controls the opening of the diode. The pulse generator may generate a plurality of pulses, each having a length of no more than 3 nanoseconds and an amplitude of at least 1 kilovolt. Electrodes may be connected to the pulse generator to deliver the plurality of pulses to biological cells.

Claims

1. Apparatus for electroperturbation of biological cells comprising:

a pulse generator configured to generate a plurality of pulses, each having a length of no more than 3 nanoseconds and an amplitude of at least 1 kilovolt; and

electrodes connected to the pulse generator configured to deliver the plurality of pulses to biological cells;

wherein the pulse generator includes a diode that is configured to operate as an opening switch and that saturates in less than 100 nanoseconds.

2. The apparatus for electroperturbation of biological cells of claim 1 wherein the pulse generator is configured to deliver the plurality of pulses at a frequency of at least 100 kHz.

3. The apparatus for electroperturbation of biological cells of claim 1 wherein the pulse generator includes a tank circuit having an admittance that is switchable from a first value to a second value that is different from the first value.

4. The apparatus for electroperturbation of biological cells of claim 1 wherein the pulse generator includes a saturable core transformer configured to operate as a switch.

5. The apparatus for electroperturbation of biological cells of claim 4, wherein said saturable core transformer controls the opening of the diode.

6. The apparatus for electroperturbation of biological cells of claim 3, wherein the pulse generator further comprises a switching system configured to cause the tank circuit to switch between the first value and the second value.

7. The apparatus for electroperturbation of biological cells of claim 6 wherein the switching system includes a first and a second electronic switch and wherein the first switch is configured to cause the diode to be forward biased upon closure and the second switch is configured to cause the diode to be reversed biased upon closure.

8. The apparatus for electroperturbation of biological cells of claim 6 wherein the diode is configured to be forward biased and reverse biased at different times and the switching system is configured to cause the admittance of the tank circuit to be at the first value while the diode is forward biased and to be at the second value while the diode is reverse biased.

9. The apparatus for electroperturbation of biological cells of claim 6 wherein the first value of the admittance is approximately half of the second value.

10. The apparatus for electroperturbation of biological cells of claim 6 wherein the tank circuit includes a first and a second capacitance and a first and a second inductance.

11. The apparatus for electroperturbation of biological cells of claim 10 wherein the product of the first capacitance and the first inductance is approximately the same as the product of the second capacitance and the second inductance.

12. The apparatus for electroperturbation of biological cells of claim 10 wherein the diode is configured to be forward biased and reverse biased at different times and the switching system is configured to:

include the first and the second capacitance and the first and the second inductance in the tank circuit while the diode is forward biased; and

include the second capacitance and the second inductance in the tank circuit, but not the first capacitance and the first inductance, while the diode is reverse biased.

13. The apparatus for electroperturbation of biological cells of claim 10 wherein the switching system is configured to transfer charge from the first capacitance to the second capacitance.

14. The apparatus for electroperturbation of biological cells of claim 13 wherein the diode is configured to be forward biased and reverse biased at different times and the switching system is configured to transfer charge only while the diode is forward biased.