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T. Tang et al.: Diode Opening Switch Based Nanosecond High Voltage Pulse Generators for Biological and Medical Applications

Diode Opening Switch Based Nanosecond High Voltage Pulse Generators for Biological and Medical Applications
Tao Tang, Fei Wang, Andras Kuthi, and Martin A. Gundersen
Department of Electrical Engineering-Electrophysics, University of Southern California Los Angeles, CA 90089-0271, USA

ABSTRACT
Studies of short (few ns) pulse cell electroperturbation require high-voltage nanosecond pulses delivered to low-impedance (10 ) electroporation cuvette loads. Here we present two pulse generators for these applications. The generators comprise of three stages of pulse modulation: an LC resonant stage switched by IGBT/MOSFET; a magnetic pulse compression stage; and a diode opening switch output stage. The all-solid-state design results in reproducible pulses and reliable, long-life operation. Pulses produced by the LC resonant stage are compressed using nonlinear properties of the magnetic material. The compressed pulses are fed to the diode opening switch, which is constructed by series and parallel connecting ordinary automotive rectifying diodes. Two versions of the pulse generator are described: The first version is capable of generating 20 ns wide, 4.5 kV amplitude pulses of 20 Hz repetition rate. A second version generates 5 ns, 7.5 kV amplitude pulses into the same 10 cuvette load. Index Terms Diode opening switch, magnetic pulse compression, electroperturbation, biological application.

1 INTRODUCTION
SIMULATION of the responses of biological cells exposed to high voltage pulses suggests that when the pulse rise time and duration are shortened to nanosecond range, intracellular structures such as the nuclei and mitochondria can be affected, possibly without adversely affecting the outer cell membrane. These effects are named here as electroperturbation, or nanoelectroperturbation, referring to the use of nanosecond pulses, in contrast with traditional electroporation, which typically involves opening of pores on the outer cell membrane, either temporarily or permanently [1]. Typically, a strong electrical field, >3-10 MV/m, is also necessary to overcome the cross membrane potential for such effects to take place. These relatively new studies of pulse effects on biological cells have stimulated a need for compact high voltage nanosecond pulse generators with readily variable output parameters [2]. A pulse generator called nanopulser using fast recovery diode as opening switch was designed for microscopic study of electroperturbation and presented in an early publication [3]. The load for this generator is a microchamber, which has electrodes of 200 m separation and 50 impedance. In order to stimulate electroperturbation effect, the generator was able to deliver 1 kV and 30 A pulses to the chamber. For further investigation of electroperturbation, large number of cells need to be exposed to
Manuscript received on 1 October 2006, in final form 13 November 2006.

high electric field, using standard cuvette as load. In order to get similar high field in the larger gap (1mm), lower impedance (10 ) cuvette, higher output voltage and current is needed from the pulse generator. It is expected, that longer but still nanosecond range pulses with smaller amplitudes produce similar effects to shorter, higher amplitude pulses. Here, we present two pulse generators capable of delivering pulses of 4.5 kV 20 ns and 7.5 kV 5 ns, respectively, to the cuvette load.

2 20 NS PULSER DESIGN
The circuit diagram of the 20 ns pulse generator is shown in Figure 1a. The system consists of 3 functionally distinct stages: an LC resonant charge stage, a magnetic pulse compression stage, and a diode opening switch stage. In the design, the pulses generated in LC resonant stage (3 kV, 1 s) are compressed to 180 ns by a saturable inductor L1. A saturable transformer T2 transfers the 180 ns pulses by forward current through the diode into a storage capacitor C2. The transformer then saturates, and a 560A, 90ns reverse current pulse results that flow through the diodes. At the peak of the reverse current, the diode will function as an opening switch, and commutes the current into the load, forming the 4.5 kV amplitude, 20 ns wide output pulse. A photograph of the pulse generator is shown in Figure 1b. The stage-by-stage design starts from calculating pulse parameters at the load and working back to the LC resonant stage.

1070-9878/07/$25.00 2007 IEEE

IEEE Transactions on Dielectrics and Electrical Insulation

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(a)
300 VDC IGB PowerEx CM300HA-12H Gnd

Cch=1.38 uF

C2 10 nF 3 x 11 Diode chain 10 oh Gnd

C1 10 nF T1 Ferrit 1:10 Gnd T2 Ferrit 4:

(b) Cuvette load Connector to Vdc

Cuvette holder

Build-in V-I probe

Figure 1. (a) Circuit diagram of the first version pulse generator. (b) Constructed first version pulse generator with a cuvette load.

2.1 ELECTRICAL CHARACTERISTICS OF CUVETTE LOAD The pulse generator is developed here for a standard electroporation cuvette, as shown in Figure 1b. The electrodes of the cuvette are of aluminum, having dimensions 1 cm 2.5 cm. The electrodes are separated by a gap of 1 mm. During the experiment, the chamber defined by the electrodes and plastic wall is filled with a nutrient solution in which various biological cells are suspended. At the frequency spectrum of the pulses generated, the load impedance ZL is approximately 10 . In order to generate a 10 MV/m electric field in the chamber, pulses with 10 kV in amplitude are required. Accordingly, the maximum output current needs to be 1 kA. These extreme numbers are for the 5 ns pulse generator. The longer, 20 ns pulse version needs to generate only ~5 MV/m field, so the voltages and currents are halved, resulting in a required 5 kV output amplitude and ~500 A peak current. Considering a near-triangular pulse having a width of 20 ns, the maximum energy delivered per pulse is approximately 50 mJ. 2.2 DIODE OPENING SWITCH STAGE Diode opening switch (DOS) reported previously by Rukin and coworkers [4,5,6] have been shown to produce as short as a few nanoseconds reverse recovery after pumping with an electron-hole plasma by a forward current pulse under special conditions. The specially designed and constructed diode can be used as opening switch, and can hold-off high voltage (tens of kV), and switch high current (few hundred A to ~1 kA).

Instead of the custom built special diodes, mass manufactured MURS2510 automotive rectifiers (1 kV, 25 A, dc rating) are used in the designs reported here. In order to rapidly turn off, the diode needs to be forward pumped in a very short period of time. Otherwise, when a diode is fully saturated by forward current, it will suffer a long reverse recovery time, which is the interval from diode current reverse flowing to turning off of the diode. The reverse recovery time is normally in hundreds of nanoseconds range, which will make the output pulse width significantly longer. Maximum forward pumping time is defined as the longest diode forward conducting time without fully saturating the diode. It indicates the longest pulse which the diode can compress efficiently. The larger this value is, the faster the diode can switch. This value is about 200 ns for a single MURS2510 diode. In order to hold an output voltage of 10 kV, a chain of eleven diodes in series is constructed. Three diode chains are connected in parallel to reduce a pre-pulse pedestal caused by the resistive phase during the forward pumping time. The diode block shows switching performance degradation in comparison with a single diode. The maximum forward pumping time drops to about 100 ns for a single chain, presumably because of the diode capacitance reduction. The actual current through diode is shown in Figure 2. The amplitude of the current is close to the designed value and the pumping time is slightly longer. This results typically in lowering the output amplitude, and increasing pulse widths relative to the design values due to parasitic inductance as discussed in the next section.

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T. Tang et al.: Diode Opening Switch Based Nanosecond High Voltage Pulse Generators for Biological and Medical Applications

2.3 SATURABLE CORE TRANSFORMER The output energy comes from current stored in the inductor formed by the secondary winding of a saturated transformer, T2. According to the current and energy values calculated previously, inductance of the saturated secondary is determined to be 400 nH (Lsat2). The saturable transformer generates the forward and reverse pumping required by the diode stage. Due to a compression ratio of 2 in the saturable transformer [3], the diode reverse conducting time is ~90 ns, which is also a quarter period of the Lsat2, C2 resonant circuit [3]. Based on this, the final storage capacitance C2 needs to be 10 nF and the peak charging voltage across C2 is ~3 kV. The transformer is wound on a CMD5005 ferrite core from Ceramic Magnetics. According to the datasheet, the core will work over a wide frequency range to 100 MHz. The dimensions of the core are OD = 50.8 mm, ID = 25.4 mm, H = 12.7 mm. The core saturates at Bsat = 0.33 T. The saturated permeability is ~4. In order to obtain Lsat2 = 400 nH, 5 turns for the secondary winding is needed. The primary winding is also 5 turns, since a 1:1 turn ratio is required. In actual circuit construction, the leakage inductance of the transformer contributes to the total inductance as well as the parasitic inductance of the diode chain and the PCB trace. So the primary and secondary windings are wound close to each other in order to reduce leakage inductance. The actual number of turn was reduced to 4 turns for both primary and secondary windings for best performance. Figure 2 shows experimental data for a forward pumping time of 182 ns and a reverse pumping time of 58 ns. The peak forward and reverse current are 256 A and 560 A, respectively, which is close to the design value. The difference is caused by overall parasitic circuit elements, mostly inductance, and timing shifts introduced by core bias shifts.
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Since the saturable transformer has a 1:1 turn ratio, the capacitor C1 in the magnetic compression stage has the same value as C2 to match the impedance and achieve maximum energy transfer. C1 discharges through the saturable inductor L1 into C2 through transformer T2. The charge transfer time is a half period of the LC series resonant circuit ( L1 C1 C 2 (C1 + C 2 ) ), which is also the forward pumping time (180 ns) of the diode stage. This determines the seriescombined transformer leakage inductance and saturated inductance of L1. This total inductance can be inferred from the current waveform in Figure 2, to be ~700 nH. To achieve a high compression ratio, a core with large saturation magnetic flux density (Bsat) is preferred. Finemet core from MK-Magnetics is chosen for its large Bsat (1.23 T) and high working frequency. The external dimension of the core is OD = 50.8 mm, ID = 25.4 mm, H = 12.7 mm. Calculation suggests 7 turns on the core for correct forward pumping. With 7-turn winding, the inductor will saturate in about 1.3 s, which is the minimum charge transfer time for the L-C resonant stage. During construction of the pulse generator, it was found that the inductor L1 saturated early with 7 turns. There are two ways to solve this problem: increasing the effective Bsat by biasing the core to the opposite direction of saturation; or increasing number of turns. To simplify the design, the second method was adopted and 2 more turns was added to the winding. In the first version pulse generator, the compression stage compresses 1 s pulse into 180 ns, which gives a compression ratio of about 5. 2.5 L-C RESONANT CHARGING An L-C resonant stage is used to generate pulses on C1 required by magnetic compression stage. The main dc power supply voltage is 300 V, which suggests the adoption of a 1:10 ratio step-up transformer to raise the voltage to the required 3 kV across C1. The transformer will match the effective capacitance of primary to secondary to get maximum energy transfer, which gives for the primary capacitor a value of Cch = 1 F. Considering the losses in the transfer, a slightly large value (1.38 F) was selected. The leakage inductance of the transformer dominates the total inductance, and determines the pulse width. By trial and error, an actual number of 1:10 was found to meet the timing requirement. Based on the previous data, the switch on the primary side needs to hold 300 V and handle a peak current of about 600 A. To fulfill the specification, an IGBT (CM300HA-12H) from PowerEx is selected.

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3 5 NS PULSER DESIGN
Figure 2. Current through diode D and voltage cross D. Forward current: 256 A, 182 ns; Reverse current: 560 A, 58 ns.

2.4 MAGNETIC COMPRESSION STAGE The output of the magnetic compression stage feeds into the primary of the saturable transformer T2. So the output pulse of this stage should have a width of 140 ns and amplitude of 3 kV.

The first version of design presented covers the range of electric fields up to 4.5 MV/m and can only give pulses of about 20 ns and 4.5 kV for 10 cuvette load. The design is modified in several aspects in order to produce shorter and larger amplitude pulses. Figure 3a shows the circuit diagram of the modified pulse generator. The photo of the constructed pulse generator is shown in Figure 3b.

IEEE Transactions on Dielectrics and Electrical Insulation

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L 2 Ferrite core 8 turns L 1 Ferrite core 4 turns

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1 kVDC MOSFET 1kV, 300A Gnd

Cch=200 nF

C3 10 nF 9 x 10 Diode chain 10 ohm Gnd

C1 10 nF T1 Nanocrystal 2:8

C2 10 nF

L 1 Ferrite core 2 turns

(b)

Figure 3. (a) Circuit diagram of the 5 ns pulse generator. (b) Photo of the 5 ns pulse generator.

In order to shorten the pulse width and increase amplitude, the system is modified in the following three aspects: (1) The LC resonant circuit is optimized to generate shorter initial pulse; (2) The saturable transformer is replaced by two saturable inductors to gain independent control of forward and reverse pumping times; and (3) more diode chains are put in parallel to relax the forward pumping requirement and further reduce the pre-pulse pedestal. 3.1 MODIFICATION OF THE DIODE OPENING SWITCH STAGE As discussed previously, the switching property of the diode degrades after series combination. The resistive loss during the forward conducting phase also increases with number of diode in series. To compensate for the effect caused by a series connection, a diode block consisting of 9 parallel diode chains is used. By adopting this diode block, the energy transfer efficiency during forward pumping increases and a pre-pulse pedestal during reverse pumping is significantly decreased. Although adoption of more parallel chains improves the switching performance, which relaxes the requirement on short forward pumping time, the effect is limited. Using the new diode unit, maximum forward pumping time was improved to 130 ns, which is slightly shorter than the 3 parallel chains design used in the other version (100 ns) but not as good as a single diode (200 ns). Further research is in progress to fully understand the effect of series/parallel combination on diode switching properties. 3.2 MODIFICATION OF THE SATURABLE TRANSFORMER STAGE In the previous design, the forward and reverse pumping of the diode stage is controlled by the saturable transformer T2. In

order to gain independent control, two individual saturable inductors (L2, L3) are used. Here the forward pumping time is determined by the resonant circuit formed by C2, C3 and saturated L2, while the reverse time is determined by C3 and saturated L3. By varying the number of turns in L2 and L3, the timing can be easily tuned. In the short pulse design, another set of winding is added to L2 and L3. dc current is passed through the winding, which will reset the cores to the opposite direction of saturation. This reset circuit not only makes the performance of the inductor more stable from pulse to pulse, but also increases the effective magnetic flux swing. The increase of magnetic flux swing lead to less number of turns for the same saturation timing and less saturated inductance. With these modifications, the forward and reverse times met the design requirements of 100 ns and 50 ns respectively.

3.3 MODIFICATION OF THE L-C RESONANT STAGE A shorter initial pulse needs less compression to get the required output pulse width. The two main factors slowing the pulse are the switching speed of the IGBT switch and the L-C resonant frequency. In the shorter pulse design, the IGBT switch is replaced by fast MOSFET switch (APT10035 from Advanced Power Technology). To reduce the LC constant, a dc input voltage is increased to 1 kV to reduce the turn ratio in T1 (1:3 in new design). With a smaller turn ratio, both the leakage inductance and the effective capacitance on the primary are reduced while the coupling coefficient is increased. The nanocrystal (FT-3) core has a high permeability at the working frequency.

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T. Tang et al.: Diode Opening Switch Based Nanosecond High Voltage Pulse Generators for Biological and Medical Applications

Comparing with the previous design, the width of initial pulse reduces from 1.5 s to 700 ns.

55 50

4 OPERATION
Both systems are powered with a high voltage dc source connected with an isolation resistor. Both pulse generators have been tested at repetition rates of 20 Hz. Typical outputs of both versions on a cuvette load with 85 l RPMI are shown in Figure 4. For the longer pulse version, the pulse amplitude is 4.6 kV and the FWHM is 18.4 ns as shown in Figure 4a. The short pulse version produces 7.5 kV and 5ns pulses as shown in Figure 4b.
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15 Figure 5. Output pulse amplitude and width vs different charging voltage for first version pulse generator

5 CONCLUSION
Two nanosecond diode pulse generators are designed and constructed for a low impedance biological load. The first version, generates 20 ns 4.5 kV pulses on a 10 ohm load. The second version shortens the pulse width to 5 ns and increases the amplitude to 7.5 kV. Automotive rectifying diodes were successfully used as nanosecond opening switches under short pumping condition. In the short pulse version, a structure with two saturable inductors is introduced to replace the normal saturable transformer configuration, and independent control over diode forward/reverse pumping can be achieved.
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ACKNOWLEDGMENT
Vmax: 7.44 kV PW : 4.8 ns

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This work was funded by the Compact-Pulsed Power MURI program funded by the Director of Defense Research and Engineering (DDR&E) and managed by the Air Force Office of Scientific Research (AFOSR).

2
[1] [2]

REFERENCES
E. Neumann, A. E. Sowers and C. A. Jardan, Electroporation and Electrofusion in Cell Biology, Plenum Press, New York, NY, 1989. A. Kuthi, T. Vernier, X. Gu and M. A. Gundersen, Compact nanosecond pulse generator for cell electroperturbation experiments, IEEE 25th Intern. Power Modulator Conf., pp. 354-357, 2002. A. Kuthi, P. Gabrielson, M. Behrend and M. Gundersen, Nanosecond Pulse Generator Using a Fast Recovery Diode, IEEE 26th Power Modulator Conf., San Francisco, CA, pp. 603-606, 2004. S. K. Lyubutin, G. A. Mesyats, S. N. Rukin and B. G. Slovikovskii, "Repetitive Nanosecond All-Solid-State Pulsers Based on SOS Diodes", IEEE 11th Intern. Pulsed Power Conf., Baltimore, Maryland, pp. 992998, 1997. S. N. Rukin, High-Power Nanosecond Pulse Generators Based on Semiconductor Opening Switches (review), Instruments and Experimental Techniques, Vol. 42, No. 4, pp. 439-467, 1999. A.I. Bushlyakov, A. V. Ponomarev, S. N. Rukin, B. G. Slovikovsky, and S. P. Timoshenkov, A Megavolt Nanosecond Generator with a Semiconductor Opening Switch, Instruments and Experimental Techniques, Vol. 45, No. 2, pp. 213-219, 2002.

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Figure 4. Output pulse to the cuvette load: (a) 4.56 kV, 18.4 ns FWHM on first version; (b) 7.44 kV, 4.8ns on the improved version

[5] [6]

By varying the charging voltage in certain range, different output amplitudes can be achieved without affecting the output pulse width significantly. In Figure 5, this effect is shown for the longer pulse generator.

Pulse Width (ns)

IEEE Transactions on Dielectrics and Electrical Insulation

Vol. 14, No. 4; August 2007

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Andrs Kuthi received the Ph.D. degree in physics from The Royal Institute of Technology, Stockholm, Sweden, in 1981. Dr. Kuthi is currently Research Scientist in the Electrical Engineering - Electrophysics Department of the University of Southern California. His current research interests are in pulsed power generators and gas phase high-voltage, high current, fast switching devices. Martin A. Gundersen (M74SM83F91) received the B.A. degree from the University of California, Berkeley, in 1965, and the Ph.D. degree from the University of Southern California, Los Angeles, in 1972. He is a Professor in the Department of Electrical Engineering-Electrophysics, University of Southern California.

Tao Tang (S04) was born in Hubei, China in 1979. He received the B.S. degree in electronic engineering from Beijing Institute of Technology, China, in 2001. Since 2001, he has been in the Ph.D. program in the Department of Electrical Engineering- Electrophysics, University of Southern California, Los Angeles. His current research projects focused on design and implementation of pulsed power systems for biological, medical and combustion ignition applications. Fei Wang (M03) received the Ph.D. degree from the University of Southern California, Los Angeles, in 2006. He is a Senior Engineer and Researcher in Alpha & Omega Semiconductor Inc. at Sunnyvale. His Ph.D. study was concentrated on design and implementation of nanosecond pulsed power systems for aircraft engine ignition and combustion control. Now he is working one test equipment design and integration for advanced power MOSFET design and developments. He authored and co-authored 30 papers. Dr. Wang is also a member of American Institute of Aeronautics and Astronautics (AIAA) and American Physical Society (APS).