High-voltage, highly efficient sine wave generator that prevents spikes during amplitude adjustment and channel switching

Abstract

This application describes various techniques for generating a high-voltage sinusoidal signal that allows for rapid adjustment of the output voltage without introducing high-frequency artifacts at the output. When these techniques are used, stronger electric fields can be applied to the tumor for a greater percentage of the time, which can enhance the effectiveness of TTFields therapy. In some embodiments, this is achieved by preventing adjustments to the DC power supply during the time that the DC power supply's output is powering the output signal. In some embodiments, this is achieved by synchronizing the operation of an AC voltage generator and an electronic switch connected to the output of the AC voltage generator.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application Nos. 62 / 955,673 (filed December 31, 2019) and 62 / 981,875 (filed February 26, 2020), each of which is incorporated by reference in its entirety. [Background technology]

[0002] The use of TTFields therapy to treat tumors is described in US Patent No. 7,805,201. TTFields therapy uses high-voltage sinusoidal signals. Originally, these high-voltage sinusoidal signals were obtained by generating a low-amplitude signal using a function generator, amplifying the low-voltage signal to a high-voltage signal using a linear amplifier, and then applying the high-voltage signal to a set of electrodes (also called a transducer array) placed on the patient's body. US Patent No. 9,910,453 describes an alternative approach for generating the high-voltage sinusoidal signal that is applied to the transducer array, which offers dramatically improved efficiency over the original linear amplifier approach. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] U.S. Patent No. 7,805,201 [Patent Document 2] U.S. Patent No. 9,910,453 Summary of the Invention [Problem to be solved by the invention]

[0004] This application describes various techniques for generating a high voltage sinusoidal signal whose output voltage can be rapidly adjusted without introducing high frequency artifacts (e.g., voltage spikes) at the output. When these techniques are used, stronger electric fields can be applied to the tumor for a greater percentage of the time, which can enhance the effectiveness of TTFields therapy. [Means for solving the problem]

[0005] One aspect of the invention is directed to a first apparatus for generating a sine wave of frequency f. The first apparatus includes a DC power supply having a voltage control input for setting an output voltage of the DC power supply, a transformer having a primary side and a secondary side, and a power switch. The power switch has a control input, the power switch configured to apply the output of the DC power supply to the primary side of the transformer in a first direction when a first control signal is applied to the control input, to apply the output of the DC power supply to the primary side of the transformer in a second direction when a second control signal is applied to the control input, and to remain off when neither the first control signal nor the second control signal is applied to the control input. The second direction is opposite to the first direction. The first device also includes a controller programmed to (a) apply a first control signal to the control input for a duration of T / 3, then (b) wait for a duration of T / 6, then (c) apply a second control signal to the control input for a duration of T / 3, then (d) wait for a duration of T / 6, then continuously repeat the sequence (a), (b), (c), and (d). T is the reciprocal of frequency f. And the first device also includes an output filter connected to the secondary side of the transformer, the output filter passing frequency f and attenuating frequencies above a cutoff frequency. The controller is further programmed to control the amplitude of the sine wave of frequency by adjusting a third control signal applied to a voltage control input of the DC power source, and the controller is further programmed to prevent the adjustment of the third control signal from occurring when either the first control signal or the second control signal is applied to the control input.

[0006] In some embodiments of the first apparatus, the cutoff frequency is between 2f and 4f and the output filter has a transfer function that has a zero at 5f.

[0007] Another aspect of the invention is directed to a second apparatus for generating a sine wave of frequency f. The second apparatus comprises n DC power supplies, each of the n DC power supplies having a voltage control input that sets an output voltage of the respective power supply, where n is a positive integer. The second apparatus also comprises a power switch having an output terminal and a control input. The power switch is configured to (a) route the output of a selected one of the n DC power supplies to the output terminal with a selected polarity in response to 2n states of a control signal applied to the control input, or (b) remain off in response to additional states of the control signal. The second device further comprises a controller programmed to control the generation of an oversampled version of the sine wave, sampled N times per cycle with equally spaced samples including a sampling point at 0°, where N=2+4n, by setting the output voltages of the n DC power supplies to levels present in the oversampled version of the sine wave, and then routing each of the n DC power supplies to an output terminal of the power switch with a selected polarity at an appropriate time in the sequence to generate the oversampled version of the sine wave by sequencing a control signal through the 2n states and an additional state. And the second device also comprises an output filter for filtering a current coming from the output terminal of the power switch. The output filter passes frequency f and attenuates frequencies above a cutoff frequency. The controller is programmed to control the amplitude of the sine wave by adjusting the output voltages of the n DC power supplies via the voltage control input, and the controller is further programmed not to adjust the output voltages of the DC power supplies while the outputs of the DC power supplies are routed to the output terminal of the power switch.

[0008] Some embodiments of the second apparatus further comprise a transformer having a primary side connected to the output terminal of the power switch and a secondary side connected to the output filter, the transformer being configured such that current from the output terminal of the power switch reaches the output filter through the transformer.

[0009] Some embodiments of the second device further include a transformer having a primary side connected to the output terminal of the power switch and a secondary side connected to the output filter, the transformer being configured such that a current from the output terminal of the power switch reaches the output filter through the transformer. In these embodiments, n=1, meaning that there is only a single DC power source. In these embodiments, the controller is programmed to control the generation of the oversampled version of the sine wave by (a) applying a first control signal to the control input for a duration of T / 3 to cause the power switch to route the output of the single DC power source to the output terminal with a first polarity, then (b) waiting for a duration of T / 6, then (c) applying a second control signal to the control input for a duration of T / 3 to cause the power switch to route the output of the single DC power source to the output terminal with a second polarity opposite to the first polarity, then (d) waiting for a duration of T / 6, then continuously repeating the sequence (a), (b), (c), and (d). T is the reciprocal of the frequency f. Optionally, in these embodiments, the cutoff frequency is between 2f and 4f, and the output filter has a transfer function that has a zero at 5f.

[0010] In some embodiments of the second apparatus, n>1, and the controller is further programmed to control the amplitude of the sine wave by adjusting the output voltages of the n DC power supplies via the voltage control inputs while maintaining a constant ratio between the output voltages of each of the n DC power supplies. Optionally, in these embodiments, the output filter may have a transfer function that has zeros at frequencies where harmonics of frequency f are expected to contain power.

[0011] Another aspect of the invention is directed to a first method for generating a sine wave of frequency f. The first method includes the steps of setting n DC power supplies to their respective output voltages, where n is a positive integer, and generating an oversampled version of the sine wave, sampled N times per cycle using equally spaced samples that include a sampling point at 0°, where N=2+4n, by setting the output voltages of the n DC power supplies to levels present in the oversampled version of the sine wave, and then switching the outputs of the n DC power supplies to outputs in a controlled sequence, such that each of the n DC power supplies is switched to output in each direction at the appropriate time in the sequence to generate the oversampled version of the sine wave. The first method also includes filtering the oversampled version of the sine wave to pass frequency f and attenuate frequencies above a cutoff frequency, where the filtering implements a transfer function that has zeros at frequencies where harmonics of frequency f are expected to contain power. The amplitude of the sine wave is controlled by regulating the output voltages of the n DC power supplies, and regulation of the output voltage of any given one of the DC power supplies is prevented while the given one of the DC power supplies is switched to output.

[0012] In some examples of the first method, n=1, meaning that there is only a single DC power supply, and regulation of the output voltage of the single DC power supply occurs only during times when the output of the single DC power supply is not switched to the output.

[0013] In some examples of the first method, the filtering implements a transfer function that has zeros at frequencies where harmonics of frequency f are expected to contain power.

[0014] Another aspect of the invention is directed to a third apparatus for generating an output waveform at a frequency f. The third apparatus comprises a first DC power supply having a first voltage control input that sets an output voltage of the first DC power supply, and a second DC power supply having a second voltage control input that sets an output voltage of the second DC power supply. The third apparatus also comprises a power switch having an output terminal and a control input. The power switch is configured to (a) route an output of the first DC power supply to the output terminal with a first polarity in response to a first state of the control input, (b) route an output of the first DC power supply to the output terminal with a second polarity in response to a second state of the control input, (c) route an output of the second DC power supply to the output terminal with the first polarity in response to a third state of the control input, (d) route an output of the second DC power supply to the output terminal with a second polarity in response to a fourth state of the control input, and (e) remain off in response to an additional state of the control input. The second polarity is opposite to the first polarity. The third device also includes an output filter for filtering a current coming from an output terminal of the power switch. The output filter passes a frequency f and attenuates frequencies above a cutoff frequency. The third device also includes a controller programmed to operate in a first mode in which the controller sets the control input to a first and second state in an alternating sequence while holding the first voltage control input constant. The controller is further programmed to operate in a second mode in which the controller sets the control input to a third and fourth state in an alternating sequence while holding the second voltage control input constant. The controller is further programmed such that when the controller is operating in the first mode, the controller causes a change in the amplitude of the output waveform by adjusting the second voltage control input and then switching the controller to the second mode, and the controller is further programmed such that when the controller is operating in the second mode, the controller causes a change in the amplitude of the output waveform by adjusting the first voltage control input and then switching the controller to the first mode.

[0015] In some embodiments of the third apparatus, the output waveform is a sine wave, and setting the control input to the first and second states in an alternating sequence includes (a) placing the control input in the first state for a duration of T / 3, then (b) waiting for a duration of T / 6, then (c) placing the control input in the second state for a duration of T / 3, then (d) waiting for a duration of T / 6, then continuously repeating the sequence (a), (b), (c), and (d), and setting the control input to the third and fourth states in an alternating sequence includes (e) placing the control input in the third state for a duration of T / 3, then (f) waiting for a duration of T / 6, then (g) placing the control input in the fourth state for a duration of T / 3, then (h) waiting for a duration of T / 6, then continuously repeating the sequence (e), (f), (g), and (h). T is the reciprocal of the frequency f.

[0016] In some embodiments of the third apparatus, the controller is further programmed to, when the controller is operating in the first mode, cause a change in amplitude of the output waveform by adjusting the second voltage control input at least 1 millisecond before switching the controller to the second mode, and the controller is further programmed to, when the controller is operating in the second mode, cause a change in amplitude of the output waveform by adjusting the first voltage control input at least 1 millisecond before switching the controller to the first mode.

[0017] Some embodiments of the third device further comprise a transformer having a primary side connected to an output terminal of the power switch and a secondary side connected to an output filter, the transformer configured such that a current from the output terminal of the power switch reaches the output filter through the transformer. Optionally, in these embodiments, the power switch may be configured to (a) route the output of the first DC power source in a first direction to the primary side of the transformer in response to a first state of the control input, (b) route the output of the first DC power source in a second direction to the primary side of the transformer in response to a second state of the control input, (c) route the output of the second DC power source in the first direction to the primary side of the transformer in response to a third state of the control input, (d) route the output of the second DC power source in a second direction to the primary side of the transformer in response to a fourth state of the control input, and (e) remain off in response to a fifth state of the control input. The second direction is opposite to the first direction.

[0018] In some embodiments of the third apparatus, the cutoff frequency is between 2f and 4f and the output filter has a transfer function that has a zero at 5f.

[0019] Another aspect of the invention is directed to a second method for generating an output waveform at a frequency f. The second method includes the steps of (a) routing the output of the first DC power supply to the output terminal of the power switch with a first polarity in response to a first state of a control input of the power switch, (b) routing the output of the first DC power supply to the output terminal with a second polarity in response to a second state of the control input, (c) routing the output of the second DC power supply to the output terminal with the first polarity in response to a third state of the control input, (d) routing the output of the second DC power supply to the output terminal with the second polarity in response to a fourth state of the control input, and (e) remaining off in response to an additional state of the control input. The second polarity is opposite to the first polarity. The second method also includes filtering the current coming from the output terminal of the power switch. The filtering includes passing the frequency f and attenuating frequencies above a cutoff frequency. The second method also includes operating in a first mode in which the control input is set to a first and second state in an alternating sequence while holding the output voltage of the first DC power supply constant. The second method also includes operating in a second mode in which the control input is set to a third and fourth state in an alternating sequence while holding the output voltage of the second DC power supply constant. In the first mode, a change in the amplitude of the output waveform is caused by adjusting the output voltage of the second DC power supply and then switching to the second mode. And, in the second mode, a change in the amplitude of the output waveform is caused by adjusting the output voltage of the first DC power supply and then switching to the first mode.

[0020] In some examples of the second method, the output waveform is a sine wave and the control input is set to the first and second states in an alternating sequence by (a) placing the control input in a first state for a duration of T / 3, then (b) waiting for a duration of T / 6, then (c) placing the control input in a second state for a duration of T / 3, then (d) waiting for a duration of T / 6, then continuously repeating the sequence (a), (b), (c), and (d). In these examples, the control input is set to the third and fourth states in an alternating sequence by (e) placing the control input in a third state for a duration of T / 3, then (f) waiting for a duration of T / 6, then (g) placing the control input in a fourth state for a duration of T / 3, then (h) waiting for a duration of T / 6, then continuously repeating the sequence (e), (f), (g), and (h), where T is the inverse of the frequency f in these examples.

[0021] In some examples of the second method, in the first mode, the change in amplitude of the output waveform is caused by adjusting the output voltage of the second DC power supply at least 1 millisecond before switching to the second mode, and in the second mode, the change in amplitude of the output waveform is caused by adjusting the output voltage of the first DC power supply at least 1 millisecond before switching to the first mode.

[0022] Another aspect of the invention is directed to a fourth apparatus for generating an AC electrical signal for application to a first pair of electrodes and a second pair of electrodes. The fourth apparatus comprises an AC voltage generator having an output, an electronic switch, and a controller. The electronic switch has an input that receives the output of the AC voltage generator, a first power output, and a second power output. The electronic switch is configured to operate (a) in a first mode that routes the output of the AC voltage generator to the first power output, and (b) in a second mode that routes the output of the AC voltage generator to the second power output. The electronic switch is further configured to cycle through a repeating sequence that includes the first mode and the second mode. The controller is configured to synchronize the operation of the AC voltage generator and the electronic switch such that whenever the electronic switch switches to either the first mode or the second mode, the instantaneous output of the AC voltage generator is less than 5V in magnitude. Within 20 milliseconds after the electronic switch switches to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of the steady state output voltage of the AC voltage generator.

[0023] In some embodiments of the fourth apparatus, the electronic switch is further configured to (c) operate in a third mode in which the output of the AC voltage generator is not routed to either the first power output or the second power output, and (d) cycle through the first mode, the second mode, and the third mode in the following repeating sequence: (1) the first mode, (2) the third mode, (3) the second mode, and (4) the third mode. In some embodiments of the fourth apparatus, the controller is configured to synchronize operation of the AC voltage generator and the electronic switch such that whenever the electronic switch switches to either the first mode or the second mode, the instantaneous output of the AC voltage generator is less than 1 V in magnitude.

[0024] In some embodiments of the fourth apparatus, within 5 milliseconds after the electronic switch switches to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of the steady-state output voltage of the AC voltage generator. In some embodiments of the fourth apparatus, within 1 millisecond after the electronic switch switches to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of the steady-state output voltage of the AC voltage generator.

[0025] In some embodiments of the fourth apparatus, during transition of the electronic switch to either the first mode or the second mode, the AC voltage generator continues to operate at its full steady-state AC output voltage.

[0026] In some embodiments of the fourth apparatus, the controller synchronizes the operation of the AC voltage generator and the electronic switch by controlling the timing of the transitions of the electronic switch such that the transitions coincide with a window of time during which the instantaneous output of the AC voltage generator is less than 5V in magnitude. In some embodiments of the fourth apparatus, the controller synchronizes the operation of the AC voltage generator and the electronic switch by controlling the AC voltage generator such that the output of the AC voltage generator is turned off whenever a transition of the electronic switch occurs. In some embodiments of the fourth apparatus, the controller synchronizes the operation of the AC voltage generator and the electronic switch by both (a) controlling the timing of the transitions of the electronic switch such that the transitions coincide with a window of time during which the instantaneous output of the AC voltage generator is less than 5V in magnitude, and (b) controlling the AC voltage generator such that the output of the AC voltage generator is turned off whenever a transition of the electronic switch occurs.

[0027] In some embodiments of the fourth apparatus, the electronic switch is configured to cycle through the first mode and the second mode in the following repeating sequence: (1) the first mode, (2) the second mode. In these embodiments, the electronic switch is configured to switch directly from the first mode to the second mode and directly from the second mode to the first mode.

[0028] Another aspect of the invention is directed to a fifth apparatus for generating an AC electrical signal for application to a first pair of electrodes and a second pair of electrodes. The fifth apparatus comprises an AC voltage generator having an output, an electronic switch, and a controller. The electronic switch has an input for receiving the output of the AC voltage generator, a first power output, and a second power output. The electronic switch is configured to (a) operate in a first mode routing the output of the AC voltage generator to the first power output, and (b) operate in a second mode routing the output of the AC voltage generator to the second power output. The electronic switch is further configured to cycle through a repeating sequence including the first mode and the second mode. The controller is configured to synchronize the operation of the AC voltage generator and the electronic switch such that whenever the electronic switch switches to either the first mode or the second mode, the instantaneous output of the AC voltage generator has a magnitude below a threshold at which the subject being treated begins to feel a perceptible sensation. Within 20 milliseconds after the electronic switch switches to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of the steady state output voltage of the AC voltage generator.

[0029] In some embodiments of the fifth apparatus, the electronic switch is further configured to (c) operate in a third mode in which the output of the AC voltage generator is not routed to either the first power output or the second power output, and (d) cycle through the first mode, the second mode, and the third mode in the following repeating sequence: (1) the first mode, (2) the third mode, (3) the second mode, and (4) the third mode.

[0030] In some embodiments of the fifth apparatus, the controller is configured to synchronize operation of the AC voltage generator and the electronic switch such that whenever the electronic switch switches to either the first mode or the second mode, the instantaneous output of the AC voltage generator is less than 1 V in magnitude.

[0031] In some embodiments of the fifth apparatus, within 5 milliseconds after the electronic switch switches to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of the steady-state output voltage of the AC voltage generator. In some embodiments of the fifth apparatus, within 1 millisecond after the electronic switch switches to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of the steady-state output voltage of the AC voltage generator.

[0032] In some embodiments of the fifth apparatus, during transition of the electronic switch to either the first mode or the second mode, the AC voltage generator continues to operate at its full steady-state AC output voltage.

[0033] In some embodiments of the fifth apparatus, the controller synchronizes the operation of the AC voltage generator and the electronic switch by controlling the timing of transitions of the electronic switch such that the transitions coincide with a window of time during which the instantaneous output of the AC voltage generator has a magnitude below the threshold. In some embodiments of the fifth apparatus, the controller synchronizes the operation of the AC voltage generator and the electronic switch by controlling the AC voltage generator such that the output of the AC voltage generator is turned off whenever a transition of the electronic switch occurs. In some embodiments of the fifth apparatus, the controller synchronizes the operation of the AC voltage generator and the electronic switch by both (a) controlling the timing of transitions of the electronic switch such that the transitions coincide with a window of time during which the instantaneous output of the AC voltage generator has a magnitude below the threshold, and (b) controlling the AC voltage generator such that the output of the AC voltage generator is turned off whenever a transition of the electronic switch occurs.

[0034] In some embodiments of the fifth apparatus, the electronic switch is configured to cycle through the first mode and the second mode in the following repeating sequence: (1) the first mode, (2) the second mode. In these embodiments, the electronic switch is configured to switch directly from the first mode to the second mode and directly from the second mode to the first mode. [Brief description of the drawings]

[0035] [Figure 1] FIG. 1 is a block diagram of a first embodiment of a sine wave generator for generating a sine wave of a preset frequency f with a controllable amplitude. [Diagram 2] FIG. 1 is a block diagram of one preferred approach for implementing a power switcher and a suitable architecture for implementing an output filter. [Diagram 3] FIG. 1 illustrates a sine wave and an oversampled version of the sine wave sampled six times per cycle. [Figure 4] FIG. 2 is a schematic diagram of an embodiment of an output filter. [Diagram 5] FIG. 2 is a block diagram of a second embodiment of a sine wave generator for generating a sine wave of a preset frequency f with a controllable amplitude. [Figure 6] FIG. 6 is a block diagram of one preferred approach for implementing a power switcher in the embodiment of FIG. 5. [Figure 7] FIG. 1 illustrates a sine wave and an oversampled version of the sine wave sampled 10 times per cycle. [Figure 8] FIG. 1 illustrates a sinusoidal output waveform under steady state conditions. [Figure 9] FIG. 13 illustrates how the sinusoidal output waveform changes when the output of a DC-DC converter being used to power the sinusoidal output changes at a particular time in the cycle. [Figure 10] FIG. 13 illustrates how the sinusoidal output waveform changes when the output of a DC-DC converter being used to power the sinusoidal output changes at different times in the cycle. [Figure 11] FIG. 11 is a block diagram of a third embodiment of a sine wave generator for generating a sine wave with controllable amplitude. [Figure 12] 12A-12C are waveform diagrams illustrating how the embodiment of FIG. 11 facilitates rapid changes to the voltage of the output signal. [Figure 13] FIG. 1 is a block diagram of a prior art system for applying TTFields to the human head. [Figure 14] FIG. 14 is a timing diagram illustrating the ordering between the two directions LR and AP used in the prior art system of FIG. [Figure 15] FIG. 1 illustrates a waveform containing a significant spike. [Figure 16A] FIG. 16 illustrates a prior art approach to avoid the spikes of FIG. 15 by ramping the AC generator output voltage up and down with 1 second intervals between switching events. [Figure 16B]FIG. 16B is a schematic diagram of the instantaneous output voltage of an AC generator using the ramp rate shown in FIG. 16A. [Figure 17A] FIG. 17 illustrates what happens when the technique of FIG. 16 is used with an interval of 0.25 seconds between switching events. [Figure 17B] FIG. 17B is a schematic diagram of the instantaneous output voltage of an AC generator using the ramp rate shown in FIG. 17A. [Figure 18] FIG. 1 illustrates an embodiment for synchronizing the operation of an AC voltage generator and a switch. [Figure 19] FIG. 19 is a timing diagram illustrating ordering between the two directions for the embodiment of FIG. 18. [Figure 20] FIG. 19 illustrates a first approach for achieving synchronization between the AC voltage generators and the switches in the embodiment of FIG. 18, which operates by precisely coordinating the switching of the switches. [Figure 21] 19 illustrates a second approach for achieving synchronization between the AC voltage generator and the switch in the embodiment of FIG. 18, which operates by controlling the output of the AC voltage generator. [Figure 22] FIG. 22 illustrates how the output of an AC voltage generator instantly jumps to its full steady-state output voltage when the approach of FIG. 21 is used. [Diagram 23] FIG. 19 illustrates another approach for achieving synchronization between the AC voltage generators and the switches in the embodiment of FIG. 18, which operates by precisely coordinating the switching of the switches. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0036] Various embodiments are described in detail below with reference to the accompanying drawings, in which like reference numerals represent like elements, and in which:

[0037] When using prior art approaches to generate a high voltage sinusoidal signal in conjunction with TTFields therapy, high frequency artifacts (e.g., voltage spikes) may appear at the output under certain conditions (e.g., in response to a command to change the output voltage or when the direction of the TTFields is switched). And because those high frequency artifacts can cause unpleasant sensations to a person being treated with TTFields therapy, the output voltage amplitude was typically ramped up slowly to prevent those high frequency artifacts (and the resulting unpleasant sensations) from occurring. However, using a slow ramp-up has a disadvantage, namely, the output voltage is not always as high as possible, which means that the electric field applied to the tumor is not always as strong as possible. Also, if the electric field is not as strong as possible, the effectiveness of the treatment may be reduced. The embodiments described herein can advantageously increase the output voltage amplitude much more quickly without introducing high frequency artifacts. Thus, these embodiments can prevent the unpleasant sensations from occurring without an associated reduction in the effectiveness of the treatment.

[0038] The embodiments described herein are useful in connection with generating TTFields as described in U.S. Patent No. 7,805,201, which is incorporated herein by reference. The embodiments described herein are based on the architecture described in U.S. Patent No. 9,910,453, which is incorporated herein by reference. In particular, the embodiments described herein allow the voltage of the sinusoidal signal (applied to the TTFields transducer array) to be adjusted more quickly without the risk of introducing high frequency artifacts (e.g., voltage spikes) at the output. The embodiments described herein also allow the sinusoidal signal to be switched on and off instantly to full power without the risk of introducing high frequency artifacts at the output.

[0039] When generating the high voltage signal for TTFields delivery, it is important to note that the exact shape of the signal is known at each point in time (a pure sine wave of known frequency) and it is only the amplitude of the output signal that varies over time based on external inputs (e.g., control based on the patient's skin temperature).

[0040] The embodiments described herein generate a high voltage sine wave signal by generating a specific pulse train that, when filtered using a specific low pass filter, results in a low distortion sine wave of a desired amplitude and frequency.

[0041] 1 is a block diagram of a first embodiment of a sine wave generator that generates a sine wave with controllable amplitude at a preset frequency f. Ultimately, the amplitude of the output sine wave will be proportional to the output of a DC power supply 50, which is preferably a controlled DC-DC converter.

[0042] In the illustrated embodiment, the DC-DC converter 50 is configured to multiply the analog voltage control input signal by 10, so that with proportional control therebetween, when a voltage control signal of 1V is applied, the output will be 10V, and when a voltage control signal of 5V is applied, the output will be 50V. Thus, the output of the DC-DC converter 50 can be any value between 0V and 50V, depending on the voltage (e.g., 0-5V) applied to the analog voltage control input. The controller 40 controls the output voltage of the DC-DC converter 50 by writing a control word to a digital-to-analog converter (DAC) 42. The DAC 42 then generates an analog voltage proportional to the control word, which is applied to the voltage control input of the DC-DC converter 50.

[0043] The output of the DC-DC converter 50 is routed to a power switcher 60. The power switcher 60 has a control input and routes the output of the DC-DC converter 50 to the primary side of the transformer 70 in either direction depending on the state of the control input. More specifically, when a first control signal is applied to the control input, the power switcher 60 applies the output of the DC-DC converter 50 to the primary side of the transformer 70 in a first direction. When a second control signal is applied to the control input, the power switcher 60 applies the output of the DC-DC converter 50 to the primary side of the transformer 70 in a second direction opposite the first direction. When neither the first control signal nor the second control signal is applied to the control input, the power switcher 60 remains off, in which case power from the DC-DC converter 50 is not routed to the primary side of the transformer 70.

[0044] FIG. 2 includes a block diagram of one preferred approach for implementing the power switcher 60 using a set of four electronically controlled switches 61-64 connected in an H-bridge configuration to the primary side of the transformer 70. These switches 61-64 open and close in response to a signal applied to a control input 68. As will be appreciated by those skilled in the relevant art, a wide variety of techniques may be used to implement these switches. For example, the switches 61-64 may be implemented using MOSFET transistors (e.g., BSC109N10NS3 manufactured by Infineon) with appropriate logic to switch them on and off in response to a control signal. To apply the output of the DC-DC converter 50 to the primary side of the transformer 70 in a first direction, only switches 63 and 62 should be closed. To apply the output of the DC-DC converter 50 to the primary side of the transformer 70 in the opposite direction, only switches 61 and 64 should be closed. If all four of these switches 61-64 are off, no power is routed to the primary side of the transformer 70.

[0045] Transformer 70 is preferably a step-up transformer having a step-up ratio between 1:4 and 1:9. In some preferred embodiments, transformer 70 is a step-up transformer having a step-up ratio of 1:6. For example, if a transformer having a step-up ratio of 1:6 is used in combination with a DC-DC converter 50 capable of outputting up to 24V, the resulting voltage at the secondary side of transformer 70 can be as high as 300V.

[0046] Returning to Figure 1, the controller 40 applies control signals to the control inputs of the power switcher 60 in a time-choreographed sequence to construct an oversampled version of a sine wave sampled six times per cycle using equally spaced samples. More specifically, Figure 3 shows a sine wave 110 and an oversampled version 112 of that sine wave sampled at 0°, 60°, 120°, 180°, 240°, 300°, and 360°. Looking at this oversampled version 112, it can be seen that it contains only three voltage levels: a positive voltage +V between 60° and 180°, a negative voltage -V between 240° and 360°, and zero volts between 0° and 60° and also between 180° and 240°. Note that the zero volt level is present because the sampling times were selected such that one of the sampling points occurs at 0°, where the sine function equals zero, and another of the sampling points occurs at 180°, where the sine function equals zero. This selection advantageously reduces the number of voltage levels that must be generated to construct the oversampled version of the sine wave 112. It also advantageously reduces the number of switching events, which minimizes losses that occur during the switching process.

[0047] As a result, an oversampled version of a sine wave at a preset frequency f can be constructed at the output of the transformer 70 by successively repeating the following four steps: (a) applying a first control signal to the control input 68 for a duration of T / 3, which corresponds to the 60-180° segment of the waveform 112 in FIG. 3, then (b) waiting for a duration of T / 6, which corresponds to the 180-240° segment of the waveform 112, then (c) applying a second control signal to the control input 68 for a duration of T / 3, which corresponds to the 240-360° segment of the waveform 112, then (d) waiting for a duration of T / 6, which corresponds to the 0-60° segment of the waveform 112. Note that T is the reciprocal of the preset frequency f.

[0048] The controller 40 is responsible for generating these control signals in this sequence. The controller 40 may be implemented using a wide variety of approaches that would be apparent to one of ordinary skill in the relevant art, including, but not limited to, a microcontroller or microprocessor programmed to perform the functions described herein. The controller 40 may also be implemented using a microcontroller or microprocessor in combination with a hardwired sequencer, which may be implemented using, for example, a state machine or counter.

[0049] The output of the secondary side of transformer 70 is routed to an output filter 80 that has a cutoff frequency between 2f and 4f. Output filter 80 passes a preset frequency, f, and attenuates frequencies above the cutoff frequency.

[0050] Note that when the oversampled version of the sine wave (112 in FIG. 3) is transformed into the frequency domain, all even harmonics become zero as a result of the fact that the waveform 112 is symmetrical. In addition, since sampling is performed six times per period, the third harmonic of the waveform 112 also becomes zero.

[0051] Many filter designs have inherent instabilities at their cutoff frequencies. However, since the third harmonic content of the oversampled waveform 112 is zero, the lowest harmonic that will have any significant power will be the fifth harmonic. If the output filter 80 is designed so that its cutoff frequency coincides with the third harmonic, the waveform will not contain power at 3f, and so the oversampled waveform 112 will not be affected by instabilities near the cutoff frequency. Therefore, it is most preferable to design the output filter 80 with its cutoff frequency at 3f, where (a) the fundamental component will be sufficiently lower than the cutoff frequency so as not to activate instability, and (b) the fifth harmonic will be sufficiently higher than the cutoff frequency so as not to activate instability.

[0052] To further reduce higher harmonics, the output filter 80 is preferably designed such that the transfer function of the output filter has a zero located at the fifth harmonic. This can be achieved, for example, by selecting components in the output filter 80 to implement an elliptic low-pass filter or a Chebyshev-2 low-pass filter. Typically, elliptic and Chebyshev-2 filters are not suitable for filtering a square wave into a sine wave, since they have significant ripples in the stop band. As a result, if the incoming signal happens to contain a frequency component that coincides with a crest in that ripple, that component will not be filtered out of the incoming signal. The embodiment of FIG. 1 avoids this situation by generating an oversampled waveform 112 at a preset frequency, which means that the frequency of the fifth harmonic is known in advance. Selecting components in the output filter 80 such that its transfer function has a zero at the fifth harmonic ensures that the fifth harmonic never coincides with a crest in a ripple in the stop band.

[0053] To reduce higher harmonics even further, output filter 80 can be designed such that its transfer function has an additional zero located at the seventh harmonic. Again, since the frequency of the seventh harmonic is known in advance, components within output filter 80 can be selected such that its transfer function has a zero at the seventh harmonic.

[0054] Designing the output filter 80 with zeros at the fifth and seventh harmonics reduces the attenuation at other frequencies located between the harmonics, which is usually highly undesirable. However, because the frequency of the oversampled waveform 112 is pre-set and contains only signals centered on odd harmonics (starting at the fifth harmonic), this design does indeed reduce the overall distortion of the output signal in the embodiment of FIG.

[0055] If the output filter 80 is designed with zeros at the fifth and seventh harmonics, the earliest harmonic containing any significant power is the ninth harmonic. However, because the power at the ninth harmonic of the oversampled waveform 112 (in FIG. 3) is relatively low to begin with, and the ninth harmonic is 6f above the cutoff frequency, the power at the ninth harmonic (and all higher harmonics) at the output 100 of the output filter 80 will be low enough to produce a good sine wave.

[0056] 2 shows a suitable architecture for implementing an output filter 80 having cutoff frequencies and zeros at the locations indicated above. Preferably, output filter 80 is a multi-stage low-pass LC filter. In this case, the first stage of output filter 80 comprises inductor 82 and capacitor 83, with subsequent stages represented by block 85. In some embodiments, filter 80 is a fourth order LC low-pass filter. In some embodiments, filter 80 is a dual M-element low-pass filter.

[0057] When the electrical characteristics of the transformer 70 are modeled, the leakage inductance of the transformer appears in series with the secondary side of the transformer 70. As a result, this leakage inductance must be taken into account when calculating the inductance of the first inductor 82 in the first stage of the output filter 80. In some embodiments, a transformer 70 is selected that has a leakage inductance large enough to provide all of the required inductance for the first inductor 82. In this case, the first inductor 82 may be completely eliminated from the output filter 80 and replaced with a wire. For example, if the calculated desired value for the first inductor in the output filter is 60 μH and the leakage inductance of the transformer 70 is 60 μH, the first inductor 82 of the output filter may be completely eliminated.

[0058] In alternative embodiments, the leakage inductance of the transformer 70 accounts for at least half of the inductance of the first stage of the low pass LC filter. In these embodiments, start with a calculated value for the first inductor 82 and reduce that value by the leakage inductance of the transformer 70. For example, if the calculated value for the first inductor in the first stage of the output filter is 100 μH and the leakage inductance of the transformer 70 is 60 μH, then a 40 μH inductor should be used as the first inductor 82 of the output filter (since 100 μH-60 μH=40 μH).

[0059] FIG. 4 is a schematic diagram of an embodiment of an output filter 80 in which the inductance of transformer 70 provides all of the necessary inductance to function as the first inductor for the first stage of the output filter. The transformer in FIG. 4 is a Zolotov TRM085 with the following characteristics: a turns ratio of 6:25, an inductance of 0.25 mH on the primary side (at 200 kHz), an inductance of 4.5 mH on the secondary side (at 200 kHz), and a leakage inductance between 32 μH and 36 μH (at 200 kHz). Capacitors C33, C35, C36, C42, C43, and C44 are all 3300 pF capacitors. C40 is a 4.7 nF capacitor. C41 is a 470 pF capacitor. Inductors L5-L8 are all 4 μH inductors. The values ​​of these components were selected to place the filter zeros at the fifth and seventh harmonics when the operating frequency was 200 kHz.

[0060] An alternative design for implementing output filter 80 having an operating frequency of 150 kHz can be realized by starting with the schematic of Figure 4 and (a) adding an additional 4.7 nF capacitor in parallel with C40, and (b) replacing the 3300 pF capacitors C33, C35, C36, C42, C43, and C44 with 5600 pF capacitors. These components were selected to place the filter zeros at the fifth and seventh harmonics when the operating frequency is 150 kHz.

[0061] The output impedance of the output filter 80 is preferably as close as possible to 70 Ohms. In an alternative embodiment, the output impedance of the output filter 80 is between 40 Ohms and 120 Ohms. Using an output impedance in this range is appropriate since the current and voltage of the output signal 100 may vary depending on the load presented (i.e., the patient and the transducer array in the context of TTFields therapy). However, because the output impedance is between 40 Ohms and 120 Ohms, even if there is a short circuit at the outlet, the current will not surge to a dangerous value. In addition, if the impedance of the load suddenly increases (e.g., if the electrodes are partially disconnected from the patient), the drop in current will be less significant. This is very useful as a safety feature in the context of TTFields therapy.

[0062] The controller 40 controls the amplitude of the output signal 100 by adjusting the control signal applied to the voltage control input of the DC-DC converter 50. In the illustrated embodiment, this is accomplished by the controller 40 writing a control word to the DAC 42. The DAC 42 responds by outputting an analog voltage that serves as the control signal applied to the voltage control input of the DC-DC converter 50. For example, assume that the output of the DAC 42 starts at 1V, the DC-DC converter is outputting 10V DC, and the transformer 70 has a 1:6 step-up ratio. Under these conditions, the pulse at the output of the secondary side of the transformer 70 will be 60V. When the controller 40 writes a new control word to the DAC 42, it causes the output of the DAC 42 to rise to 2V. The DC-DC converter 50 responds to the new signal applied to its voltage control input by increasing its output voltage to 20V DC, which causes the pulse at the output of the secondary side of transformer 70 to increase to 120V (after passing through step-up transformer 70).

[0063] Preferably, the voltage and / or current of the output signal 100 is monitored by a voltage sensing circuit 92 and / or a current sensing circuit 94. The outputs of these circuits 92, 94 are preferably fed back to the controller 40, which is preferably configured such that upon detection of an error condition at the output 100 (e.g., over-voltage, over-current, severe voltage drop, etc.), the controller 40 shuts down the power switcher 60 by inhibiting generation of both the first and second control signals applied to the control input 68 of the power switcher 60. Optionally, shutdown of the power switcher 60 may also be triggered by an over-temperature condition in the load by including appropriate temperature sensors and routing signals from these temperature sensors back to the controller 40.

[0064] It should be noted that in the illustrated embodiment, a single controller 40 is used to implement all of the control and sequencing functions described herein, however, in alternative embodiments, a programmable controller 40 may be combined with a hardwired sequencer to perform each of these two functions.

[0065] In some embodiments, the output of the current sense circuit 94 and / or the voltage sense circuit 92 are fed back to the controller 40. In these embodiments, the controller can adjust the voltage at the output of the DC-DC converter 50 by writing an appropriate control word to the DAC 42 to adjust the current or voltage of the output signal 100 to a desired level. For example, if the controller 40 is set to adjust the current to a particular level and the output of the current sense circuit 94 indicates that the current is too low, the controller can increase the voltage at the output of the DAC 42, which causes an increase in amplitude in the output signal 100. Similarly, if the output of the current sense circuit 94 indicates that the current is too high, the controller can decrease the voltage at the output of the DAC 42, which causes a corresponding decrease in amplitude in the output signal 100.

[0066] In alternative embodiments, the transformer 70 (shown in FIGS. 1 and 2) may be omitted, in which case the two conductors at the output of the power switcher 60 are directly connected to the two conductors at the input of the output filter 80. In these embodiments, current flows directly from the output of the power switcher 60 to the input of the output filter 80 without going through a transformer. However, these alternative embodiments are less preferred, especially in situations where isolation is desired and in situations where a high voltage output is desired. In addition, these alternative embodiments cannot rely on the leakage inductance of the transformer to provide some or all of the inductance required for the first stage of the filter.

[0067] 1 embodiment relies on a priori knowledge of the incoming signal and deliberate construction of both the signal and output filter 80 such that the most significant high frequencies are essentially zero (e.g., the even and third harmonics) or are made zero by output filter 80 (e.g., the fifth and seventh harmonics). This helps to provide a very clean high voltage output signal at the desired frequency with very high efficiency.

[0068] The embodiment of Figure 1 uses a single DC-DC converter 50 and implements six equally spaced sampling points per cycle. In alternative embodiments, the number of sampling points may be increased to N=2+4n, where n is a positive integer. For n=1, the situation is as described above in relation to Figure 1. For n=2, the situation is as described below in relation to Figure 5, which uses two DC-DC converters. Other embodiments may be implemented for n>2 following the same framework using additional DC-DC converters and even more samples (following the rule N=2+4n).

[0069] Figure 5 is a block diagram of a second embodiment of a sine wave generator generating a sine wave with controllable amplitude at a preset frequency f, where n=2. As a result, there are two DC-DC converters 50, 50B and 10 samples per cycle (following the formula N=2+4n) ​​are used. It should be noted that in the embodiment of Figures 5-6, components with similar reference numbers operate in a similar manner to that described above in relation to the embodiment of Figures 1-2.

[0070] FIG. 7 shows a sine wave 120 and an oversampled version 122 of that sine wave sampled ten times per cycle (i.e., at 0°, 36°, 72°, ... 324°, and 360°). Looking at this oversampled version 122, it can be seen that it contains only five voltage levels: a low positive voltage +V1, a higher positive voltage +V2, a low negative voltage -V1, a higher negative voltage -V2, and zero volts (between 0° and 36°, and between 180° and 216°). Again, the zero volt level exists because the sampling times were selected such that one of the sampling points occurs at 0°, where the sine function equals zero, and another one of the sampling points occurs at 180°, where the sine function equals zero. This selection advantageously reduces the number of voltage levels that must be generated to build the oversampled version 122 of the sine wave into two levels (i.e., V1 and V2).

[0071] As a result, the controller 40B can be used to control the generation of an oversampled version of a sine wave, sampled N times per cycle using equally spaced samples including a sampling point at 0°, where N=2+4n, by setting the output voltages of the DC power supplies to levels present in the oversampled version of the sine wave, and then sequencing the control signals through the 2n states plus an additional off state, so that each of the DC power supplies is applied to the primary of the transformer in each direction at the appropriate time in the sequence to generate the oversampled version of the sine wave.

[0072] For n=2 (as in the embodiment of FIGS. 5-6), an oversampled version of a sine wave of a preset frequency f may be constructed at the output of the transformer 70 by continuously repeating the following eight steps: apply V1 to the primary of the transformer 70 in a first direction between 36° and 72°, apply V2 in a first direction between 72° and 144°, apply V1 in a first direction between 144° and 180°, stay off between 180° and 216°, apply V1 in a second direction between 216° and 252°, apply V2 in the second direction between 252° and 324°, apply V1 in the second direction between 324° and 360°, and stay off between 0° and 36°. Note that for the resulting waveform to properly track the oversampled version of the sine wave (122 in FIG. 7), the ratio between V1 and V2 must remain constant. More specifically, the ratio V2 / V1 must be equal to sin(72°) / sin(36°), which is 1.618.

[0073] Controller 40B is responsible for generating control signals that cause power switcher 60B to apply these voltages to transformer 70 in the sequence specified above. Controller 40B is similar to controller 40 in the embodiment of Figure 1, except that controller 40B sequences through 10 states per cycle instead of 6 states per cycle.

[0074] Referring now to FIG. 6, power switch 60B has a control input 68, and the power switch is configured to (a) apply the output of a selected one of the DC power sources to the primary of transformer 70 in a selected direction in response to 2n states of a control signal applied to the control input 68, or (b) remain off in response to additional states of the control signal.

[0075] FIG. 6 is a block diagram of one preferred approach for implementing the power switcher 60B. This power switcher is similar to the power switcher 60 of the embodiment of FIG. 1, except that it includes additional switches 65-66 for switching the output of the second DC-DC converter across the transformer 70 in either direction. More specifically, this power switcher 60B uses a set of six electronically controlled switches 61-66 connected to the primary side of the transformer 70, as shown in FIG. 6. These switches 61-66 (similar to the corresponding switches in the embodiment of FIGS. 1-2) open and close in response to a signal applied to a control input 68. To route the output of the first DC-DC converter 50 to the primary side of the transformer 70 in a first direction, only switches 63 and 62 should be closed. To route the output of the first DC-DC converter 50 to the primary side of the transformer 70 in the opposite direction (i.e., with the opposite polarity), only switches 61 and 64 should be closed. To route the output of the second DC-DC converter 50B in a first direction to the primary side of the transformer 70, only switches 65 and 62 should be closed. To route the output of the second DC-DC converter 50B in the opposite direction (i.e., with the opposite polarity) to the primary side of the transformer 70, only switches 61 and 66 should be closed. If all six of these switches 61-66 are off, no power is routed to the primary side of the transformer 70.

[0076] Returning to FIG. 5, an output filter 80B is connected to the secondary side of the transformer 70, where the output filter passes a preset frequency f and attenuates frequencies above the cutoff frequency. The output filter 80B is similar to the output filter 80 in the embodiment of FIGS. 1-2, except that the location of zeros in the transfer function of the output filter 80B must be adjusted to account for the different frequency content of the oversampled waveform 122 (shown in FIG. 7). More specifically, the output filter 80B should have a transfer function that has zeros at frequencies where harmonics of the preset frequency f are expected to contain power.

[0077] For example, since the waveform 122 has 10 samples per cycle, the earliest harmonic expected to appear is the 9th harmonic. Therefore, a transfer function that has a zero at the 9th harmonic is useful when this waveform 122 is being used. The cutoff frequency of the filter should also be adjusted accordingly based on the set of harmonics expected to appear (which may be pre-calculated by taking a Fourier transform of the waveform being used).

[0078] Optionally, the transfer function of the output filter 80B can also be designed to have a zero at the next frequency where a harmonic of the preset frequency f is expected to contain power. In the case of waveform 122, this is the 11th harmonic.

[0079] The controller 40B controls the amplitude of the sine wave at the output 100B of the output filter 80B by adjusting the output voltages of the DC power supplies 50, 50B via their voltage control inputs while maintaining a constant ratio between the output voltages of each of the DC power supplies. In the illustrated embodiment, this is accomplished by writing appropriate control words to DAC42 and DAC42B, taking care to maintain the required ratio of sin(72°) / sin(36°), as explained above. In an alternative embodiment, the second DAC42B could be eliminated and replaced with a 1.618× hardware multiplier inserted between the output of DAC42 and the voltage control input to the second DC-DC converter 50B.

[0080] In alternative embodiments, the transformer 70 may be omitted from the embodiment of Figure 5, in which case the two conductors at the output of the power switcher 60B are directly connected to the two conductors at the input of the output filter 80B. In these embodiments, current flows directly from the output of the power switcher 60B to the input of the output filter 80B without passing through a transformer. However, these embodiments are less preferred for the same reasons discussed above in connection with Figure 1.

[0081] It should be noted that the system described above is suitable for generating high voltage signals of any shape, so long as the pulse train resulting in the high voltage signal can be determined prior to use, either by calculation or experiment, and the filters designed accordingly.

[0082] When the output signal generated by the system is applied to electrodes to generate TTFields (as described in patent 7,805,201), changes in the load associated with the patient's body and the transducer array can change the output signal by interacting with the output filter. This means that any change to this load (e.g., lifting the disk off the patient's body, shorting it, etc.) will immediately affect the output signal, which is constantly monitored. It is therefore possible for the device to respond very quickly to these changes (e.g., by shutting down the power switcher 60 in response to the detection of a short circuit or overload condition).

[0083] In particular, since the above described embodiments generate sine waves at known frequencies, the exact shape of the desired output signal is known in advance at each point in time. It is only the amplitude of the output signal that varies over time based on the controller responding to external inputs (e.g., current or temperature measurements). The above described embodiments may advantageously be used to generate very clean narrow band limited signals in the frequency range of 100-500 kHz with very low losses and very low sensitivity to the external load to which the signal generator is connected.

[0084] In alternative embodiments, the system may be used to generate sine waves of any desired frequency within a preset range by constructing a filter using components with adjustable reactance (e.g., adjustable capacitance or adjustable inductance). In these embodiments, the reactance of the adjustable components is set to imbue the filter with the desired transfer function characteristics. An appropriate oversampled sine wave is then generated and fed to the filter, as discussed above in connection with Figures 1 and 5.

[0085] In other alternative embodiments, the system may be used to generate a finite number of predefined signals at multiple different preset frequencies. These embodiments may be implemented by storing the pulse train characteristics for each of the predefined signals in a look-up table and providing a bank of filters that can be selectively switched into the signal path to provide the filtering characteristics required to generate a desired one of the predefined signals. When using the system to generate one of the predefined signals, the characteristics of the required pulse train are retrieved from memory and the appropriate filter (i.e., one that matches this pulse train) is switched into the signal path.

[0086] In other alternative embodiments, a composite signal containing a small number of discrete frequencies (e.g., between two and five frequencies) may be generated by generating an oversampled version of the composite signal and passing the oversampled version of the composite signal through an appropriate filter.

[0087] 1 and 5 described above, depending on the structure of the DC-DC converters 50 / 50B, high frequency artifacts (e.g., spikes) may appear at the output 100 / 100B when the output voltages of those DC-DC converters change (e.g., when the controller 40 / 40B writes a new control word to the DAC 42 / 42B). Also, high frequency artifacts may cause unpleasant sensations in a person being treated with TTFields therapy, so it is desirable to take steps to prevent such high frequency artifacts.

[0088] One suitable approach to prevent high frequency artifacts from appearing in the output 100 / 100B is to intentionally slow down the response time of the DC-DC converters 50 / 50B (e.g., by adding a sufficiently large capacitor across the output of each DC-DC converter). However, this approach, although effective, has two drawbacks: first, additional components must be included in the circuit; and second, slowing down the response time of the system prevents the output voltage from changing abruptly in situations where abrupt changes may be desirable.

[0089] 8-10 show an alternative approach to preventing high frequency artifacts from appearing in the output 100 / 100B without artificially slowing the response time of the DC-DC converter 50 / 50B.

[0090] More specifically, Figure 8 shows the same waveform 112 described above in connection with Figure 3 (appearing at the output of power switcher 60 in Figure 1) and a sinusoidal output waveform 115 (appearing at the output 100 of output filter 80 in Figure 1) under steady state conditions (e.g., when the voltage at the output of DC-DC converter 50 in Figure 1 is held at a constant 20V DC, meaning that controller 40 in Figure 1 is not updating the contents of DAC 42). In this steady state condition, output waveform 115 behaves as described above in connection with Figures 1-4 and does not contain any high frequency artifacts.

[0091] FIG. 9 shows how things change when a DC-DC converter with a fast response time is used and the output of DC-DC converter 50 (shown in FIG. 1) changes from 20V DC to 40V DC. As explained above in connection with FIG. 1, controller 40 can initiate this change by updating the contents of DAC 42 at time t9. Before this time t9, output waveform 215 is identical to output waveform 115 in the example of FIG. 8. However, as soon as controller 40 updates the contents of DAC 42 at time t9, the output of DAC 42 is applied to the voltage control input of DC-DC converter 50, so that the output voltage of the DC-DC converter begins to change rapidly (e.g., from 20V to 40V in the illustrated example). And because power switch 60 is set to actively source current from DC-DC converter 50 to transformer 70 at that moment t9, the rapid change in current passes through transformer 70 to output filter 80, which adds high frequency artifacts 215 to output 100. (Note that dashed line 222 represents a continuation of the original sine wave that was present before t9, while dashed line 220 represents a clean sine wave at twice the original amplitude.)

[0092] A similar situation exists when the design of the DC-DC converter is such that spikes and / or instability may appear at the output of the DC-DC converter in response to changes in the voltage control input of the DC-DC converter (regardless of the response time of the DC-DC converter). More specifically, if the power switch 60 is set to actively source current from the DC-DC converter 50 to the transformer 70 at the moment the voltage control input of the DC-DC converter changes, any spikes at the output of the DC-DC converter will travel through the transformer 70 to the output filter 80, which will add high frequency artifacts 215 to the output 100.

[0093] Under certain circumstances, if the output voltage of the DC-DC converter is changed during a time interval when the power switch 60 is set to actively source current from the DC-DC converter 50 / 50B to the transformer 70, high frequency artifacts may be added to the output 100. On the other hand, if the output of the DC-DC converter is changed during a time interval when the power switch 60 is not actively source current from the DC-DC converter 50 / 50B to the transformer 70, high frequency artifacts will not appear at the output 100. The controller 40 / 40B in the embodiment of FIG. 1 / FIG. 5 can take advantage of this dichotomy to prevent high frequency artifacts from appearing at the output 100 / 100B. More specifically, the controller 40 / 40B does this by ensuring that the output of the DC-DC converter 50 / 50B is changed only during an interval when the power switch 60 / 60B is not actively source current from the DC-DC converter.

[0094] 1 embodiment described above, the controller 40 achieves this by preventing regulation of the voltage control input of the DC-DC converter 50 from occurring when (a) a first control signal is applied to the control input of the power switcher 60 (i.e., when the power switcher 60 routes the output of the DC-DC converter 50 to the primary side of the transformer 70 in one direction), or (b) a second control signal is applied to the control input of the power switcher 60 (i.e., when the power switcher 60 routes the output of the DC-DC converter 50 to the primary side of the transformer 70 in the opposite direction). When neither the first nor the second control signal is applied to the control input, the power switcher 60 remains off, in which case the controller 40 can regulate the voltage control input of the DC-DC converter 50 without introducing high frequency artifacts at the output 100.

[0095] 10 illustrates how things unfold in the context of the embodiment of FIG. 1 when the output of the DC-DC converter 50 changes from 20V DC to 40V DC during time t10 when the power switch 60 is not actively sourcing current from the DC-DC converter. Prior to this time t10, the output of the DC-DC converter 50 will be at a first level (e.g., 20V in the illustrated example) and the output waveform 315 will be identical to the output waveform 115 in the example of FIG. 8. The controller 40 updates the contents of the DAC 42 at time t10 when the power switch 60 is not actively sourcing current from the DC-DC converter 50 to the transformer 70. The output voltage of the DC-DC converter 50 begins to change rapidly (e.g., from 20V to 40V in the illustrated example) and stabilizes before the power switch 60 begins routing current to the transformer 70 at t11. Because the output of DC-DC converter 50 is already stable when power switch 60 begins routing current to transformer 70 at t11, the waveform entering the output filter after t11 will be an oversampled sine wave with a different amplitude (e.g., 40V). And, when the oversampled sine wave is provided to output filter 80 as described above in connection with Figures 1-4, the resulting output 100 will be a very clean sine wave.

[0096] 5 embodiment described above, controller 40B prevents high frequency artifacts from appearing at output 100B by ensuring that the output of any given DC-DC converter 50 / 50B is only changed during intervals when power switch 60 is not actively supplying current from the given DC-DC converter. Controller 40B accomplishes this by not adjusting the output voltage of any DC power supply while its output is routed to the output terminal of power switch 60.

[0097] 11 is a block diagram of a third embodiment of a sine wave generator for generating a sine wave with controllable amplitude at a preset frequency f. Components having like reference numbers operate in a similar manner as corresponding components described above in connection with FIGS. 1-5.

[0098] This embodiment uses two DC-DC converters 51, 52. Each of these DC-DC converters is configured to multiply an analog voltage control input signal by a fixed number (e.g., 10). In this example, with proportional control between them, when a voltage control signal of 1V is applied, the output is 10V, and when a voltage control signal of 5V is applied, the output is 50V. Thus, the output of the DC-DC converters 51, 52 can be any value between 0V and 50V depending on the voltage (e.g., 0-5V) applied to the analog voltage control input. The controller 40C controls the output voltage of the DC-DC converters 51, 52 by writing a control word to the DAC 42, 42B. The DAC then generates analog voltages proportional to the control word, and these analog voltages are applied to the voltage control inputs of the DC-DC converters 51, 52.

[0099] Controller 40C is responsible for generating the control signals that cause power switcher 60B to apply these voltages to transformer 70 in the sequence described below.

[0100] Figure 6 is a block diagram of one preferred approach for implementing power switcher 60B. This power switcher is identical to power switcher 60B of the embodiment of Figure 5. More specifically, this power switcher 60B uses a set of six electronically controlled switches 61-66 connected to the primary side of a transformer 70 as shown in Figure 6. These switches 61-66 open and close in response to a signal applied to a control input 68.

[0101] To route the output of the first DC-DC converter 51 to the primary side of the transformer 70 in a first direction, only switches 63 and 62 should be closed. Power switcher 60B is configured so that this occurs in response to a first state of a control input. To route the output of the first DC-DC converter 51 to the primary side of the transformer 70 in the opposite direction (i.e., with opposite polarity), only switches 61 and 64 should be closed. Power switcher 60B is configured so that this occurs in response to a second state of the control input.

[0102] To route the output of the second DC-DC converter 52 to the primary side of the transformer 70 in a first direction, only switches 65 and 62 should be closed. The power switcher 60B is configured for this to occur in response to a third state of the control input. To route the output of the second DC-DC converter 52 to the primary side of the transformer 70 in the opposite direction (i.e., with the opposite polarity), only switches 61 and 66 should be closed. The power switcher 60B is configured for this to occur in response to a fourth state of the control input. If all six of these switches 61-66 are off, no power is routed to the primary side of the transformer 70. The power switcher 60B is configured for this to occur in response to a fifth state (also referred to herein as an additional state) of the control input.

[0103] The controller 40C has the ability to operate in either a first mode or a second mode. In the first mode, the controller 40C generates an output waveform 100C powered exclusively from the first DC-DC converter 51 by setting the control input of the power supply switcher 60B to a first and second state in an alternating sequence while holding the first voltage control input constant. In some preferred embodiments, a waveform similar to the waveform 112 in FIG. 3 can be generated by (a) placing the control input in a first state for a duration of T / 3, then (b) waiting for a duration of T / 6, then (c) placing the control input in a second state for a duration of T / 3, then (d) waiting for a duration of T / 6, then continuously repeating the sequence (a), (b), (c), and (d). The amplitude of this waveform depends only on the output voltage of the DC-DC converter 51. Filtering this waveform with output filter 80 (identical to output filter 80 in the embodiment of Figures 1-2) results in a clean sine wave (as described above in connection with Figures 1-4).

[0104] In the second mode, the controller 40C generates an output waveform 100C powered exclusively from the second DC-DC converter 52 by setting the control input of the power supply switcher 60B to a third and fourth state in an alternating sequence while holding the second voltage control input constant. In some preferred embodiments, a waveform similar to the waveform 112 in FIG. 3 can be generated by (e) placing the control input in the third state for a duration of T / 3, then (f) waiting for a duration of T / 6, then (g) placing the control input in the fourth state for a duration of T / 3, then (h) waiting for a duration of T / 6, then continuously repeating the sequence (e), (f), (g), and (h). The amplitude of this waveform depends only on the output voltage of the DC-DC converter 52. Filtering this waveform by the output filter 80 results in a clean sine wave.

[0105] FIG. 12 illustrates how the embodiment of FIG. 11 facilitates rapid changes to the voltage of the output signal 100C by switching between a first mode and a second mode. Trace 410 is the output voltage of the first DC-DC converter 51, trace 420 is the output voltage of the second DC-DC converter 52, and trace 430 is the output signal. FIG. 11 begins at t0 with the controller 40C operating in a first mode. In this mode, the output waveform 430 is powered exclusively from the first DC-DC converter 51 (set to 20V in the illustrated example). The controller 40C controls the generation of the output waveform 430 by setting the control input of the power switcher 60B to a first and second state in an alternating sequence (with wait times interspersed at appropriate times) while holding the first voltage control input constant, as described above.

[0106] While still operating in the first mode, the controller 40C predetermines what the output voltage will be when it eventually switches to the second mode. The controller 40C then issues a command at time t1 to move the output voltage of the second DC-DC converter 52 to a desired level. In the illustrated example, the desired level of the second DC-DC converter 52 is 40V. Notably, the second DC-DC converter is not being used at this time, so the reaction time of the second DC-DC converter may be very slow.

[0107] Preferably, after the output of the second DC-DC converter 52 has settled to a desired level, the controller 40C switches to the second mode. This transition from the first mode to the second mode occurs simultaneously when the power switcher 60B is in the fifth state and is not routing current to the transformer 70. In the second mode, the output waveform 430 is powered exclusively from the second DC-DC converter 52 (set to 40V in the illustrated example). The controller 40C controls the generation of the output waveform 430 by setting the control input of the power switcher 60B to the third and fourth states in an alternating sequence (with wait times interspersed at appropriate times) while holding the second voltage control input constant, as described above. Preferably, the command to initiate the change in voltage of the second DC-DC converter 52 (i.e., t1 in FIG. 12) occurs sufficiently in advance (e.g., at least 1 millisecond) before the controller 40C switches to the second mode (i.e., t2 in FIG. 12) to allow the output of the second DC-DC converter 52 to settle to the desired level so that the output waveform 430 is quickly at the desired level when the second mode begins at t2.

[0108] A similar process occurs when returning from the second mode to the first mode. More specifically, while still operating in the second mode, the controller 40C predetermines what the output voltage will be when it eventually switches to the first mode. The controller 40C then issues a command at time t3 to move the output voltage of the first DC-DC converter 51 to a desired level. In the illustrated example, the new desired level of the first DC-DC converter 51 is 10V. Notably, the first DC-DC converter is not being used at this time, so the reaction time of the first DC-DC converter may be very slow.

[0109] Preferably, the controller 40C switches to the first mode after the output of the first DC-DC converter 51 has settled to a desired level. This transition from the second mode to the first mode occurs simultaneously when the power switcher 60B is in the fifth state and is not routing current to the transformer 70. In the first mode, the output waveform 430 is powered exclusively from the first DC-DC converter 51 (set to 10V in the illustrated example). The controller 40C controls the generation of the output waveform 430 by setting the control input of the power switcher 60B to the first and second states in an alternating sequence (with wait times interspersed at appropriate times) while holding the first voltage control input constant, as described above. Preferably, the command to initiate the change in voltage of the first DC-DC converter 51 (i.e., t3 in FIG. 12) occurs sufficiently in advance (e.g., at least 1 millisecond) before the controller 40C switches to the first mode (i.e., t4 in FIG. 12) to allow the output of the first DC-DC converter 51 to settle to the desired level so that the output waveform 430 is immediately at the desired level when the first mode begins at t4.

[0110] In alternative embodiments, transformer 70 may be omitted from the embodiment of FIG. 11, in which case the two conductors at the output of power switcher 60B are connected directly to the two conductors at the input of output filter 80. In these embodiments, current flows directly from the output of power switcher 60B to the input of output filter 80 without passing through a transformer. However, these embodiments are less preferred for the same reasons discussed above in connection with FIG.

[0111] TTFields therapy involves inducing an electric field (e.g., at 200 kHz) through a targeted body part to treat tumors in the targeted body part. Experiments have shown that the efficiency of TTFields is increased when the direction of the TTFields is changed during the course of treatment. For example, in the Optune® prior art system, the direction of the TTFields is changed every second. However, in alternative embodiments, the direction can be changed at a different rate (e.g., between 50 milliseconds and 10 seconds).

[0112] FIG. 13 is a block diagram of the original Optune® prior art system for applying TTFields to a person's head (or other body part) in two different directions. This is accomplished using a pair of transducer arrays 25A, 25P positioned at the front and back (i.e., anterior and posterior) of the head, and another pair of transducer arrays 25L, 25R positioned at the left and right sides of the person's head. More specifically, when an AC voltage is applied between transducer arrays 25L and 25R, an electric field traveling primarily in the left-to-right (LR) direction is induced in the subject's head. And, when an AC voltage is applied between transducer arrays 25A and 25P, an electric field traveling primarily in the anterior-to-posterior (AP) direction is induced in the subject's head. TTFields can also be applied to other parts of the body (e.g., pancreas, lungs, etc.) by positioning transducer arrays on the subject's skin in front / back and right / left of the relevant body part.

[0113] In the embodiment of Figure 13, a single AC voltage generator 20 is used to drive both transducer array pairs (i.e., 25L / R and 25A / P). This is accomplished by routing the output of AC voltage generator 20 to switch 22. Depending on the state of a control signal, switch 22 routes the signal from AC voltage generator 20 across either one pair of transducer arrays (i.e., 25L / R) or the other pair of transducer arrays (i.e., 25A / P).

[0114] FIG. 14 is a timing diagram showing the sequence between the two directions LR and AP used in the original Optune®. In this approach, switch 22 (a) routes the output of AC voltage generator 20 to the left and right transducer arrays (25L / R) for 1 second, then (b) routes the output of AC voltage generator 20 to the anterior and posterior transducer arrays (25A / P) for 1 second, then repeats steps (a) and (b) in an alternating sequence. A short period of time (e.g., 5-10 milliseconds) during which the output of AC voltage generator 20 was not routed to either pair of transducer arrays (25L / R, 25A / P) was inserted between each step (indicated by the label OFF).

[0115] One problem that was addressed during the design of the original Optune® is described in connection with FIG. 15. More specifically, when switch 22 switches from the off state to either the LR or AP state (trace 525) while the instantaneous output voltage 520 generated by AC voltage generator 20 is substantial (e.g., >10V), the output waveform resembles trace 530, which includes spikes 532. Because such spikes 532 can be perceived as an unpleasant sensation by the subject, the original Optune® was designed to prevent such spikes from occurring. More specifically, this was accomplished by ramping the output voltage of AC voltage generator 20 down from its steady-state value to zero V during a 100 ms interval preceding each off state, and then ramping the output voltage back up to its steady-state value during a 100 ms interval following each off state, as shown in trace 540 of FIG. 16A. The ramp rate was approximately 1 V / ms, which was slow enough to avoid spikes that the patient might notice.

[0116] The resulting waveform at the output of AC voltage generator 20 was similar to that shown in FIG. 16B (except that the actual frequency of the sine wave generated by AC voltage generator 20 was orders of magnitude higher than the sine wave shown). Note that the scale of the x-axis in FIG. 16B has been expanded by a factor of four relative to FIG. 16A to show the additional detail. This solution also worked very well in the context of the original Optune®, since the system operated at its peak output voltage 80% of the time and only 20% of the time was spent ramping the voltage up, ramping the voltage down, or with the voltage turned off.

[0117] Now we investigate what happens when a similar approach is used, but the interval at which the AC voltage is applied to either the LR or AP transducer array is shortened from 1 second to 0.25 seconds. If the same 1V / ms ramp-down and ramp-up approach described above in connection with FIG. 16A is used in this new timescale, the output voltage of the AC voltage generator 20 follows trace 550 in FIG. 17A. And, as a result, the waveform at the output of the AC voltage generator 20 resembles the waveform shown in FIG. 17B (except, again, that the actual frequency of the sine wave generated by the AC voltage generator 20 is orders of magnitude greater than the sine wave shown). Note that the scale of the x-axis in FIG. 17B has been expanded by a factor of 4 relative to FIG. 17A to show additional detail.

[0118] However, this solution is less than ideal, since the peak output voltage is applied to the transducer array only 20% of the time, which means that the maximum electric field is applied to the subject only 20% of the time. Thus, unlike the prior art situation shown in Figures 16A / 16B (where the output voltage is ramped up / down to ensure patient comfort, and the ramping reduces the percentage of time spent at the peak voltage by a small amount), using the same ramp slope when the switching time is reduced to 0.25 seconds reduces the percentage of time spent at the peak voltage by a very large amount (as shown in Figures 17A / 17B). Furthermore, the situation becomes even worse if the interval during which the AC voltage is applied to either the LR or AP transducer array is reduced to less than 0.20 seconds, in which case the peak voltage (and corresponding peak electric field strength) is never reached.

[0119] The embodiment of FIG. 18 uses a different approach to avoid spikes similar to spike 532 shown in FIG. 15. More specifically, the embodiment of FIG. 18 has an AC voltage generator 30 and a switch 32, and relies on synchronization between those two functional blocks to avoid spikes, as described below in connection with FIGS. 19-23. In some preferred embodiments, the AC voltage generator 30 in FIG. 18 is implemented using the approach described above in connection with FIGS. 1-7. The switch 32 is configured to (a) route the output of the AC voltage generator 30 to the left and right transducer arrays (25L / R) in response to a first state of its control input, (b) route the output of the AC voltage generator 30 to the front and rear transducer arrays (25A / P) in response to a second state of its control input, or (c) remain off in response to a third state of its control input. The switch 32 may be implemented using any of a variety of approaches apparent to one skilled in the relevant art, including, but not limited to, a field effect transistor, a solid state relay, and the like.

[0120] In the illustrated embodiment, synchronization between the AC voltage generator 30 and the switch 32 is implemented using a synchronization controller 35 programmed to send control signals to the AC voltage generator 30 and / or the switch 32 to coordinate their components such that the signals described below are generated with the time relationships described below. Various alternative approaches for synchronizing the AC voltage generator 30 and the switch 32 may also be used. For example, synchronization may be achieved by allowing the AC voltage generator 30 to operate freely and coordinating the switching time of the switch 32 (as described below in connection with FIG. 20). Alternatively, synchronization may be achieved by allowing the switch 32 to switch automatically and turning off the AC voltage generator 30 before each switching event (as described below in connection with FIG. 21). Yet another alternative for achieving synchronization is to control the timing of both the AC voltage generator 30 and the switch 32.

[0121] FIG. 19 is a timing diagram illustrating the sequencing between the two directions LR and AP for the embodiment of FIG. 18. In this embodiment, the switch 32 (a) routes the output of the AC voltage generator 30 to the left and right transducer arrays (25L / R) for duration T, then (b) routes the output of the AC voltage generator 30 to the front and rear transducer arrays (25A / P) for duration T, then repeats steps (a) and (b) in an alternating sequence. A short period of time (e.g., 5-10 ms) during which the output of the AC voltage generator 30 is not routed to either pair of transducer arrays is inserted between each step (indicated by the label OFF). This can be choreographed by repeatedly adjusting the control input of the switch 32 to cycle through the LR mode, AP mode, and OFF mode in the following repeating sequence: (1) LR mode, (2) OFF mode, (3) AP mode, and (4) OFF mode.

[0122] In this embodiment, the duration T can be much shorter than 1 second because the output voltage of the voltage generator 30 is not slowly ramped up and down (as in the prior art embodiment described above in connection with FIG. 16). Instead, the output of the AC voltage generator 30 either stays at its full value all the time (as described below in connection with FIG. 20) or jumps to its full value immediately after the switch 32 switches state (as described below in connection with FIG. 21). In either case, the signal applied to the transducer arrays 25A / P, 25L / R is at its full value a majority of the time (e.g., >90% or >95% of the time). Keeping the TTFields stronger for a greater percentage of the time can then advantageously improve the effects of the TTFields treatment. In some embodiments, the duration T is longer than 20 milliseconds. In some embodiments, the duration T is between 0.1 and 0.5 seconds. In some embodiments, the duration T is between 0.2 and 0.3 seconds. In particular, in contrast to the situation described above in relation to Figures 17A / 17B, regardless of how short the duration of T is, the system operates at its full output voltage for a large percentage of the time.

[0123] FIG. 20 shows a first approach to achieving synchronization between the AC voltage generator 30 and the switch 32 that operates by controlling the timing of the transition of the switch 32 from an OFF state (shown by trace 635) to either the LR state or the AP state such that the transition coincides with a window of time during which the instantaneous magnitude of the output of the AC voltage generator is sufficiently small so that the jump from the OFF state to a small voltage does not cause a perceptible sensation to the subject being treated.

[0124] The voltage threshold resulting in a sensation may vary from person to person and may also depend on which part of the body is in contact with the transducer array. For example, in various parts of the body, a jump from the OFF state to either 1V, 1.5V, 2V, 2.5V, 3V, 3.5V, 4V, 4.5V, or 5V is not perceptible. Therefore, to prevent the switching from causing a perceptible sensation, the transition from the OFF state to either the LR state or the AP state should be timed to coincide with the window of time during which the magnitude of the instantaneous output of the AC voltage generator is below their thresholds. In this approach, the output voltage of the AC voltage generator 30 can remain at its full steady-state value 100% of the time, as shown by trace 630. In some preferred embodiments, the transition occurs when the instantaneous output of the AC voltage generator is less than 1V in magnitude.

[0125] For example, assume that the threshold of perception for a given subject is 5V and the output of the AC voltage generator 30 is 100V pk-pk (meaning that the instantaneous output value of the AC voltage generator 30 ranges between +50V and -50V). The instantaneous output of the AC voltage generator will be less than 5V in magnitude for the first 5.7° of each 360° cycle, the middle 11.4° of each cycle, and the last 5.7° of each cycle. By restricting the switching of the switch 32 from the OFF state to either the LR state or the AP state to these specific windows of time, the signal 640 applied to the transducer array (25L / R or 25A / P) will not have any spikes greater than 5V in magnitude, which means that they are not perceptible to the subject. It should be noted that if the AC voltage generator is operating at 200 kHz, then 11.4° corresponds to 0.16 microseconds, a window long enough to facilitate synchronization by aligning the switching of switch 32 with the specific time windows identified in this paragraph.

[0126] In some preferred embodiments, the switching of the switch 32 from the OFF state to either the LR state or the AP state is limited to those windows of time during which the instantaneous output of the AC voltage generator is less than 1V in magnitude. Assuming the same 100V pk-pk output voltage, the instantaneous output of the AC voltage generator will be less than 1V in magnitude at the first 1.1° of each cycle, the middle 2.2° of each cycle, and the last 1.1° of each cycle. By limiting the switching of the switch 32 from the OFF state to either the LR state or the AP state to these specific windows of time, the signal 640 applied to the transducer array (25L / R or 25A / P) will never have any spikes greater than 1V in magnitude. As will be appreciated by those skilled in the art, the timing of the switch 32 may be adjusted for other thresholds as well.

[0127] In the example shown in FIG. 20, the output voltage of the AC voltage generator 30 remains at its full steady-state value 100% of the time, as shown by trace 630. In this situation, the signal 640 applied to the transducer array (25L / R or 25A / P) instantly jumps to its full steady-state output voltage as soon as it is turned on. Thus, the signal applied to the transducer arrays 25A / P, 25L / R is nearly always at its full value. And, as noted above, keeping the TTFields stronger for a greater percentage of the time can advantageously improve the efficacy of TTFields treatment. However, it should be noted that the output voltage of the AC voltage generator 30 during the very beginning of the LR or AP state is not critical, and in alternative embodiments, it is acceptable if the output voltage of the AC voltage generator drops to some degree. However, the output of the AC voltage generator 30 preferably reaches at least 80% of the AC voltage generator's steady-state output voltage within 20 milliseconds after the electronic switch switches from the OFF state to either the LR or AP state. In some preferred embodiments, this occurs within 5 milliseconds, and in some preferred embodiments, this occurs within 1 millisecond.

[0128] Similar synchronization of the switching of switch 32 to a small magnitude portion of the AC voltage generator's output sine wave (i.e., less than 1 V, 1.5 V, 2 V, 2.5 V, 3 V, 3.5 V, 4 V, 4.5 V, or 5 V in magnitude) is preferably performed when switch 32 switches back to the off state from either the LR state or the AP state.

[0129] Figure 21 shows a second approach to achieving synchronization between the AC voltage generator 30 and the switch 32 in Figure 18. This approach operates by reducing the instantaneous output voltage of the AC voltage generator 30 to less than 5V in magnitude before switching the switch 32 from the OFF state to either the LR state or the AP state to prevent spikes from appearing in the conductors leading to the transducer arrays 25L / R and 25A / P when the switch 32 switches state. In some preferred embodiments, the instantaneous output voltage of the AC voltage generator 30 is reduced in magnitude to less than 1V (e.g., to 0V) before switching the switch 32.

[0130] Reducing the output voltage of the AC voltage generator 30 to 0V is easy to achieve when any of the embodiments described above in relation to Figures 1-6 and 10-12 are used as the AC voltage generator. For example, when the AC voltage generator of Figures 1 and 2 is used, its output can be set to zero by ensuring that neither the first control signal nor the second control signal is applied to the control input of the power switcher 60, which means that all switches in the power switcher 60 (i.e., switches 61-64) remain off. Similarly, when the AC voltage generator of Figures 5 and 6 is used, its output can be set to zero by sending a control signal to the power switcher 60B that switches off all switches in the power switcher 60B (i.e., switches 61-66).

[0131] In FIG. 21 , the top trace 650 shows the output of the AC voltage generator 30, the middle trace 655 shows the state of the switch 32, and the bottom trace 660 shows one of the outputs (LR or AP) of the switch 32. Assume that the switch 32 starts in the off state, and at t20, the switch 32 is set to route the output of the AC voltage generator 30 to either the LR pair 25L / R of the transducer array or the AP pair 25A / P of the transducer array. At some time before t20, a control signal is sent to the AC voltage generator 30 to reduce the output voltage of the AC voltage generator 30 to zero. When the switch 32 is switched at t20, the output of the AC voltage generator 30 is 0V, so no spikes appear on the conductors leading to the transducer arrays 25L / R and 25A / P at that time.

[0132] After a short time interval (e.g., <0.1 ms), at t21, the synchronization controller 35 (see FIG. 18) starts sending control signals (e.g., as described above in connection with FIGS. 1-6 and 10-12) to the AC voltage generator 30, which causes the AC voltage generator 30 to start generating the sine wave 650. Due to the configuration of the AC voltage generator (e.g., as described above in connection with FIGS. 1-6 and 10-12), in particular the output filter 80 / 80B in the embodiment of FIGS. 1-5, the AC voltage generator 30 does not introduce any spikes at the output 650 at t21, so that the spikes do not propagate to the output 660. Also, because the switch 32 has already settled to its current state, the switch 32 does not introduce any spikes at the output 660 (supplied to the transducer arrays 25L / R or 25A / P) at t21.

[0133] In particular, as shown in FIG. 21, the output voltage 650 of the AC voltage generator 30 preferably jumps immediately to its full steady-state output voltage without a ramp-up period. Thus, the signal applied to the transducer arrays 25A / P, 25L / R is nearly always at its full value. And, as noted above, keeping the TTFields stronger for a greater percentage of the time can advantageously improve the efficacy of TTFields therapy. FIG. 22 shows the immediate jump to the full steady-state output voltage on a longer time scale, which contrasts sharply with the prior art configuration shown in FIG. 16. However, it should be noted that the output voltage of the AC voltage generator 30 during the very beginning of the LR or AP state is not critical, and in alternative embodiments, it is acceptable for the output voltage of the AC voltage generator not to jump immediately to its full steady-state voltage. However, the output of the AC voltage generator 30 should preferably reach at least 80% of the AC voltage generator's steady-state output voltage within 20 milliseconds after the electronic switch switches from the OFF state to either the LR or AP state. In some preferred embodiments, this occurs within 5 milliseconds. And in some preferred embodiments, this occurs within 1 millisecond.

[0134] FIG. 21 also illustrates an exemplary approach for synchronizing the AC voltage generator 30 and the switch 32 when the time to switch from either the LR state or the AP state to the OFF state is reached. At time t22, the AC voltage generator 30 is generating a sine wave at its full steady-state output voltage, and the switch 32 remains set to route the output of the AC voltage generator 30 to either the LR pair of the transducer array 25L / R or the AP pair of the transducer array 25A / P. At time t23, the controller stops generating a signal (described above in connection with FIGS. 1-6 and 10-12) to the power switcher 60 / 60B, which reduces the output of the AC voltage generator 30 to 0V. Also, due to the configuration of the AC voltage generator described above, at t23, no spike appears at the output 650, which means no spike appears at the output 660 of the switch 32. After a short time interval (e.g., <0.1 ms), at t24, the switch 32 is set to the OFF state. Also, because the output of AC voltage generator 30 is 0 V at t24, no spike is introduced into the conductor extending between switch 32 and transducer array 25 at t24.

[0135] In the embodiment described above in connection with FIGS. 18 and 19, the switch 32 (a) routes the output of the AC voltage generator 30 to the left and right transducer arrays (25L / R) for duration T, then (b) routes the output of the AC voltage generator 30 to the front and rear transducer arrays (25A / P) for duration T, then repeats steps (a) and (b) in an alternating sequence. A short period of time (e.g., 5-10 ms) during which the output of the AC voltage generator 30 is not routed to either pair of transducer arrays is inserted between each step. This is choreographed by repeatedly adjusting the control input of the switch 32 to cycle through the LR mode, AP mode, and off mode in the following repeating sequence: (1) LR mode, (2) off mode, (3) AP mode, and (4) off mode.

[0136] In a variation of these embodiments, the off mode (i.e., the short period of time during which the output of the AC voltage generator 30 is not routed to either pair of transducer arrays) is omitted. In this variation, the switch 32 (a) routes the output of the AC voltage generator 30 to the left and right transducer arrays (25L / R) for duration T, then (b) routes the output of the AC voltage generator 30 to the anterior and posterior transducer arrays (25A / P) for duration T, then repeats steps (a) and (b) in a two-step alternating sequence. This is choreographed by repeatedly adjusting the control input of the switch 32 to cycle through the LR and AP modes in the following repeating sequence: (1) LR mode, (2) AP mode.

[0137] In this variation in which the off mode is omitted, the duration T can also be much shorter than 1 second for the same reasons explained above, and here again, in contrast to the situation described above in connection with Figures 17A / 17B, regardless of how short the duration of T is, the system will operate at its full output voltage for a large percentage of the time (e.g., 100% of the time).

[0138] The transitions of the switch 32 from the LR state to the AP state, and from the AP state to the LR state, are timed to coincide with a window of time during which the instantaneous magnitude of the output of the AC voltage generator is small enough so as not to cause a perceptible sensation to the subject being treated. More specifically, the transitions between the LR state and the AP state should be timed to coincide with a window of time during which the instantaneous output magnitude of the AC voltage generator is below the same thresholds described above in the embodiment of Figures 18-20, including the off state (e.g., at the first 1.1° of each cycle, the middle 2.2° of each cycle, and the last 1.1° of each cycle).

[0139] FIG. 23 shows an example of timing for synchronizing the transitions of switch 32 (shown in FIG. 18 ) between LR and AP states (shown by trace 675 in FIG. 23 ) with the output of AC voltage generator 30 (shown in FIG. 18 ) (shown by trace 670) such that the transitions between the LR and AP states coincide with the window of time during which the instantaneous magnitude of the output of AC voltage generator 30 (trace 675) is close to zero (e.g., <5V or <1V).

[0140] 18-22 advantageously allow the transducer array to be driven at full power for a much greater percentage of the time than was possible in prior art systems, without fear of introducing voltage spikes that could result in unpleasant sensations in the person being treated. Driving the transducer array at full power can also advantageously enhance the effectiveness of treatments using TTFields.

[0141] Finally, although the embodiment described above in relation to Figures 18-23 discusses switching an AC voltage between a first pair of transducer arrays located in front / back of the relevant body part and a second pair of transducer arrays located in front / back of the relevant body part, this approach may be extended to more than two pairs of transducer arrays. For example, a third pair of transducer arrays may be located above / below the relevant body part, in which case the AC voltage is switched in a repeating sequence between the first, second, and third pairs of transducer arrays in a manner similar to the switching described above in relation to Figures 18-23.

[0142] Although the present invention has been disclosed with reference to specific embodiments, numerous modifications, alterations, and variations are possible to the described embodiments without departing from the sphere and scope of the invention, as defined in the appended claims. Accordingly, it is intended that the present invention not be limited to the described embodiments, but rather have its full scope defined by the language of the following claims and equivalents thereof. [Explanation of symbols]

[0143] 20 AC voltage generator 22 Switch 25A Transducer Array 25L Transducer Array 25P transducer array 25R Transducer Array 30 AC voltage generator 32 Switch 35 Synchronous Controller 40 Controller, Programmable Controller 40B Controller 40C Controller 42 Digital-to-Analog Converter (DAC), DAC 50 DC power supply, DC-DC converter, first DC-DC converter 51 DC-DC converter, first DC-DC converter 52 DC-DC converter, second DC-DC converter 50B DC-DC converter, second DC-DC converter 60 Power Switcher 60B Power Switcher, Power Switch 61 Electronically controlled switches, switches 62 Electronically controlled switches, switches 63 Electronically controlled switches, switches 65 Electronically controlled switches, switches 66 Electronically controlled switches, switches 64 Electronically controlled switches, switches 68 Control Input 70 Transformer 80 Output Filter 80B Output Filter 82 inductor, first inductor 83 Capacitor 85 blocks 92 Voltage sensing circuit, circuit 94 Current sensing circuit, circuit 100 Output, Output Signal 100B output 100C output waveform 110 sine wave 112 oversampled version, waveform 115 Sine wave output waveform, output waveform 120 sine wave 122 oversampled version 215 Output waveform, high frequency artifacts 220 dashed line 222 dashed line 315 Output Waveform 410 Trace 420 Trace 430 traces, output waveforms 520 Instantaneous Output Voltage 525 Trace 530 Trace 532 Spike 540 Trace 550 Trace 630 Trace 635 Trace 640 signal 650 trace, sine wave, output, output voltage 655 Trace 660 Trace, Output 675 Trace

Claims

1. 1. An apparatus for generating an alternating electrical signal for application to a first pair of electrodes and a second pair of electrodes, the apparatus comprising: an AC voltage generator having an output; an electronic switch having an input to receive the output of the AC voltage generator, a first power output, and a second power output, the electronic switch configured to (a) operate in a first mode to route the output of the AC voltage generator to the first power output, and (b) operate in a second mode to route the output of the AC voltage generator to the second power output, the electronic switch further configured to cycle through a repeating sequence including the first mode and the second mode; a controller configured to synchronize operation of the AC voltage generator and the electronic switch such that whenever the electronic switch switches to either the first mode or the second mode, an instantaneous output of the AC voltage generator is less than 5V in magnitude. Equipped with within 20 milliseconds after the electronic switch switches to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of the steady state output voltage of the AC voltage generator; during transition of the electronic switch to either the first mode or the second mode, the AC voltage generator continues to operate at its full steady state AC output voltage. Device.

2. 2. The apparatus of claim 1, wherein the electronic switch is further configured to: (c) operate in a third mode in which the output of the AC voltage generator is not routed to either the first power output or the second power output; and (d) cycle through the first mode, the second mode, and the third mode in the following repeating sequence: (1) the first mode, (2) the third mode, (3) the second mode, and (4) the third mode.

3. 2. The apparatus of claim 1, wherein the controller is configured to synchronize operation of the AC voltage generator and the electronic switch such that whenever the electronic switch switches to either the first mode or the second mode, the instantaneous output of the AC voltage generator is less than 1 V in magnitude.

4. 2. The apparatus of claim 1, wherein within 5 milliseconds after the electronic switch switches to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of a steady-state output voltage of the AC voltage generator.

5. 2. The apparatus of claim 1, wherein within 1 millisecond of the electronic switch switching to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of a steady-state output voltage of the AC voltage generator.

6. 2. The apparatus of claim 1, wherein the controller synchronizes operation of the AC voltage generator and the electronic switch by controlling timing of transitions of the electronic switch such that the transitions coincide with a window of time during which the instantaneous output of the AC voltage generator is less than 5 volts in magnitude.

7. 2. The apparatus of claim 1, wherein the controller synchronizes the operation of the AC voltage generator and the electronic switch by controlling the AC voltage generator such that the output of the AC voltage generator is turned off whenever a transition of the electronic switch occurs.

8. 2. The apparatus of claim 1, wherein the controller synchronizes operation of the AC voltage generator and the electronic switch by both: (a) controlling timing of transitions of the electronic switch such that transitions coincide with windows of time during which the instantaneous output of the AC voltage generator is less than 5 volts in magnitude; and (b) controlling the AC voltage generator such that the output of the AC voltage generator is turned off whenever a transition of the electronic switch occurs.

9. 2. The apparatus of claim 1, wherein the electronic switch is configured to cycle through the first mode and the second mode in the following repeating sequence: (1) the first mode, (2) the second mode, and the electronic switch is configured to switch directly from the first mode to the second mode and directly from the second mode to the first mode.

10. 1. An apparatus for generating an alternating electrical signal for application to a first pair of electrodes and a second pair of electrodes, the apparatus comprising: an AC voltage generator having an output; an electronic switch having an input to receive the output of the AC voltage generator, a first power output, and a second power output, the electronic switch configured to (a) operate in a first mode to route the output of the AC voltage generator to the first power output, and (b) operate in a second mode to route the output of the AC voltage generator to the second power output, the electronic switch further configured to cycle through a repeating sequence including the first mode and the second mode; a controller configured to synchronize operation of the AC voltage generator and the electronic switch such that whenever the electronic switch switches to either the first mode or the second mode, an instantaneous output of the AC voltage generator has a magnitude less than a given voltage. Equipped with within 20 milliseconds after the electronic switch switches to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of the steady state output voltage of the AC voltage generator; during transition of the electronic switch to either the first mode or the second mode, the AC voltage generator continues to operate at its full steady state AC output voltage. Device.

11. 11. The apparatus of claim 10, wherein the electronic switch is further configured to: (c) operate in a third mode in which the output of the AC voltage generator is not routed to either the first power output or the second power output; and (d) cycle through the first mode, the second mode, and the third mode in the following repeating sequence: (1) the first mode, (2) the third mode, (3) the second mode, and (4) the third mode.

12. 11. The apparatus of claim 10, wherein the controller is configured to synchronize operation of the AC voltage generator and the electronic switch such that whenever the electronic switch switches to either the first mode or the second mode, the instantaneous output of the AC voltage generator is less than 1 V in magnitude.

13. 11. The apparatus of claim 10, wherein within 5 milliseconds after the electronic switch switches to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of a steady-state output voltage of the AC voltage generator.

14. 11. The apparatus of claim 10, wherein within 1 millisecond of the electronic switch switching to either the first mode or the second mode, the output voltage of the AC voltage generator is at least 80% of a steady-state output voltage of the AC voltage generator.

15. 11. The apparatus of claim 10, wherein the controller synchronizes operation of the AC voltage generator and the electronic switch by controlling timing of transitions of the electronic switch such that the transitions coincide with windows of time during which the instantaneous output of the AC voltage generator has a magnitude below the threshold.

16. 11. The apparatus of claim 10, wherein the controller synchronizes the operation of the AC voltage generator and the electronic switch by controlling the AC voltage generator such that the output of the AC voltage generator is turned off whenever a transition of the electronic switch occurs.

17. 11. The apparatus of claim 10, wherein the controller synchronizes operation of the AC voltage generator and the electronic switch by both: (a) controlling timing of transitions of the electronic switch such that transitions coincide with windows of time during which the instantaneous output of the AC voltage generator has a magnitude below the threshold, and (b) controlling the AC voltage generator such that the output of the AC voltage generator is turned off whenever a transition of the electronic switch occurs.

18. 11. The apparatus of claim 10, wherein the electronic switch is configured to cycle through the first mode and the second mode in the following repeating sequence: (1) the first mode, (2) the second mode, and the electronic switch is configured to switch directly from the first mode to the second mode and directly from the second mode to the first mode.

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