Controlling an electrical signal sent to a sample load using a pulse modulated resistance

• US 7,750,605 B2
• Filed: 09/19/2007
• Issued: 07/06/2010
• Est. Priority Date: 09/21/2006
• Status: Active Grant

• Current Assignee: Bio-Rad Laboratories Incorporated
• Original Assignee: Bio-Rad Laboratories Incorporated
• Inventors: Ragsdale, Charles W.
• Primary Examiner(s): Tso; Edward
• Assistant Examiner(s): WILLIAMS, ARUN C
• Application Number:
  US11/857,679
• Publication Number:
  US 20080106238A1
• Time in Patent Office: 1,021 Days
• Field of Search: 320/166, 320/167, 323/242
• US Class Current: 320/166
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
• CPC Class Codes: H03K 3/53 by the use of an energy-accumulating element discharged through the load by a switching device controlled by an external signal and not incorporating positive feedback H03K3/335 takes precedence

Abstract

Systems, methods, apparatus, and circuits for controlling an electrical signal transmitted to a sample load are provided. The electrical signal produced by a capacitor is controlled via a control signal sent to a variable resistance device that is connected in parallel with the sample load. The variable resistance device includes a resistance and a switch in series. The control signal opens and closes the switch, thus providing a variable resistance based on the amount of time the switch is closed.

Claims

1. A method of controlling an electrical pulse transmitted to a sample load containing biological molecules, the method comprising:

charging a capacitance;

subsequent to the charging, connecting the capacitance with the sample load and a variable resistance device connected in parallel with the sample load containing biological molecules, the variable resistance device including;

a first resistor;

a first switch connected in series with the first resistor, wherein the first switch is opened and closed by a first control signal;

transmitting an electrical pulse from the capacitance to the sample load and the variable resistance device; and

controlling the electrical pulse by opening and closing, with the first control signal, the first switch a plurality of times during transmission of the electrical pulse.

2. The method of claim 1, wherein the first control signal opens and closes the first switch such that the variable resistance device has a constant resistance while the electrical pulse is transmitted.

3. The method of claim 2, wherein the constant resistance is specified by a user.

4. The method of claim 1, wherein the first control signal is a pulse width modulated signal, wherein a resistance of the variable resistance device is controlled by the pulse width modulated signal.

5. The method of claim 1, wherein the first control signal opens and closes the first switch such that the resistance of the variable resistance device varies while the electrical pulse is transmitted.

6. The method of claim 5, wherein the first control signal is a pulse width modulated signal, and wherein the pulse widths change as to vary the resistance of the variable resistance device while the electrical pulse is transmitted.

7. The method of claim 1, wherein the electrical pulse is an exponentially decaying pulse, further comprising adjusting the first control signal to achieve a desired time constant τ

for the exponential decay.

8. The method of claim 1, wherein the electrical pulse is a pulse of a square wave.

9. The method of claim 1, wherein the variable resistance device further includes one or more other resistors in series with the first resistor.

10. The method of claim 1, wherein the variable resistance device further includes:

a second resistor connected in parallel with the first resistor; and

a second switch connected in series with the second resistor, wherein the second switch is opened and closed by a second control signal.

11. The method of claim 10, wherein the variable resistance device further includes:

one or more additional resistors, each connected in parallel with the first and second resistors and with the other additional resistors; and

one or more additional switches, each connected in series with one of the additional resistors.

12. The method of claim 1, wherein the sample load contains biological molecules that are electroporated by the electrical pulse.

27. The method of claim 1, further comprising:

transmitting one or more additional electrical pulses from the capacitance to the sample load and the variable resistance device; and

controlling the additional electrical pulses by opening and closing, with the first control signal, the first switch a plurality of times during transmission of each respective electrical pulse.

28. The method of claim 7, wherein adjusting the first control signal to achieve a desired time constant τ

includes varying a duty cycle of the first control signal such that the desired time constant τ

is achieved.

13. A circuit configured to provide a controllable electrical pulse to a sample load containing biological molecules, the circuit comprising:

a capacitance selectively connected with the sample load; and

a variable resistance device connected in parallel with the sample load containing biological molecules, the variable resistance device including;

a first resistor; and

a first switch in series with the first resistor, wherein the first switch is opened and closed by a first control signal;

wherein when the capacitance is charged and selected to be connected with the sample load, an electrical pulse is transmitted from the capacitance to the sample load and the variable resistance device, and wherein the first control signal controls the electrical pulse by opening and closing the first switch a plurality of times during transmission of the electrical pulse.

14. The circuit of claim 13, wherein the capacitance is connected in parallel with sample load.

15. The circuit of claim 13, wherein the first control signal is a pulse width modulated signal, wherein a resistance of the variable resistance device is controlled by the pulse width modulated signal.

16. The circuit of claim 13, wherein the first control signal opens and closes the first switch such that the resistance of the variable resistance device varies while the electrical pulse is transmitted.

17. The circuit of claim 13, wherein the first control signal is a pulse width modulated signal, and wherein the pulse widths change as to vary the resistance of the variable resistance device while the electrical pulse is transmitted.

18. The circuit of claim 13, wherein the electrical pulse is an exponentially decaying pulse and the first control signal is determined by a computer system to achieve a desired time constant τ

for the exponential decay.

19. The circuit of claim 13, wherein the variable resistance device further includes one or more other resistors in series with the first resistor.

20. The circuit of claim 13, wherein the variable resistance device further includes:

a second resistor connected in parallel with the first resistor; and

a second switch connected in series with the second resistor, wherein the second switch is opened and closed by the first control signal.

21. The circuit of claim 20, wherein the variable resistance device further includes:

one or more additional resistors, each connected in parallel with the first and second resistors and with the other additional resistors; and

one or more additional switches, each connected in series with one of the additional resistors.

22. An electroporator system for providing a controllable electrical pulse to a sample load containing biological molecules, comprising:

a capacitance selectively connected with the sample load; and

a variable resistance device connected in parallel with the sample load, the variable resistance device including;

a first resistor; and

a first switch in series with the first resistor, wherein the first switch is opened and closed by a first control signal;

wherein when the capacitance is charged and selected to be connected with the sample load, an electrical pulse is transmitted from the capacitance to the sample load and the variable resistance device, and wherein the electrical pulse is controlled with the first control signal by opening and closing the first switch a plurality of times during transmission of the electrical pulse, and wherein the electrical pulse causes electroporation of the biological molecules in the sample load.

23. The electroporator system of claim 22, further comprising a charging circuit that charges the capacitance to a specified voltage.

24. The electroporator system of claim 22, further comprising a switching driver that provides the first control signal that determines the resistance of the variable resistance device by opening and closing the first switch.

25. The electroporator system of claim 24, further comprising a high voltage driver for selectively connecting the capacitance to the sample load.

26. The electroporator system of claim 22, wherein the capacitance is not connected to the sample load prior to the capacitance being charged to a desired voltage and is connected to the sample load when the capacitance is charged to a desired voltage.