High Voltage Nanosecond Pulse Generator Using Fast Recovery Diodes for Cell Electro-manipulation

• US 20070031959A1
• Filed: 04/13/2006
• Published: 02/08/2007
• Est. Priority Date: 04/22/2005
• Status: Active Grant

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Kuthi, Andras, Gundersen, Martin
• Granted Patent: US 7,767,433 B2
• Time in Patent Office: Days
• US Class Current: 435/283.100
• 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. A pulse generator circuit comprising:

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.

2. The pulse generator of circuit of claim 1 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.

3. The pulse generator circuit of claim 1 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.

4. The pulse generator circuit of claim 1 wherein the first value of the admittance is approximately half of the second value.

5. The pulse generator circuit of claim 1 wherein the tank circuit includes a first and a second capacitance and a first and a second inductance.

6. The pulse generator circuit of claim 5 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.

7. The pulse generator circuit of claim 5 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.

8. The pulse generator of claim 5 wherein the switching system is configured to transfer charge from the first capacitance to the second capacitance.

9. The pulse generator of claim 8 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.

10. The pulse generator circuit of claim 1 wherein the diode saturates in less than 100 nanoseconds and the switching system includes a saturable core transformer.

11. A pulse generator circuit comprising:

a diode that that is configured to operate as an opening switch and that saturates in less than 100 nanoseconds; and

a saturable core transformer configured to operate as a switch that controls the opening of the diode.

12. The pulse generator of claim 11 further comprising a tank circuit that includes the saturable core transformer and that is in series with the diode

13. The pulse generator of claim 12 wherein the tank circuit has an admittance that is switchable from a first value to a second value that is different from the first value.

14. The pulse generator of claim 13 wherein the saturable core transformer is configured to cause the admittance to switch from the first value to the second value.

15. The pulse generator of claim 13 wherein the first value of the admittance is approximately half of the second value.

16. The pulse generator of claim 12 wherein the tank circuit include a first and a second capacitance.

17. The pulse generator of claim 16 wherein the diode is configured to be forward biased and reversed biased at different times and further comprising a MOSFET configured to cause the first and the second capacitance to be part of the tank circuit while the diode is forward biased and to cause the second capacitance to be part of the tank circuit, but not the first capacitance, while the diode is reversed biased.

18. Apparatus for electropertubation 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.

19. The apparatus for electropertubation of biological cells of claim 18 wherein the pulse generator is configured to deliver the plurality of pulses at a frequency of at least 100 kHz.

20. The apparatus for electropertubation of biological cells of claim 18 wherein the pulse generator includes a diode that is configured to operate as an opening switch and that saturates in less than 100 nanoseconds.

21. The apparatus for electropertubation of biological cells of claim 18 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.

22. The apparatus for electropertubation of biological cells of claim 18 wherein the pulse generator includes a saturable core transformer configured to operate as a switch.