AU2016250332A1

AU2016250332A1 - Electrical stimulation device

Info

Publication number: AU2016250332A1
Application number: AU2016250332A
Authority: AU
Inventors: Chi-Heng Chang; Jian-Hao Pan
Original assignee: Gimer Medical Co Ltd
Current assignee: Gimer Medical Co Ltd
Priority date: 2015-10-23
Filing date: 2016-10-24
Publication date: 2017-05-11

Abstract

The present application discloses am electrical stimulation device for electrically stimulating at least one target zone of an organism. The electrical stimulation device comprises a control unit and an electrical stimulation unit. The electrical stimulation unit includes a frequency synthesizer, an amplifier, a variable resistor, at least one first electrode and at least one second electrode. The frequency synthesizer is coupled to the control unit and generates a frequency signal. The amplifier is coupled to the frequency synthesizer. The variable resistor comprises a resistance and is coupled to the control unit and the amplifier. The first electrode and the second electrode are coupled to the amplifier. The amplifier outputs an electrical stimulation signal according to the frequency signal of the frequency synthesizer and the resistance of the variable resistor to impel the first electrode and the second electrode to generate an electric field. The electric field covers the target zone, and the electric field strength ranges from 100 V/m to 5000 V/m, so as to electrically stimulate the target zone of the organism.

Description

ELECTRICAL STIMULATION DEVICE 2016250332 24 Oct 2016

Technical Field [0001] The present invention relates to an electrical stimulation device.. Background Art Discussion [0002] The human nerves are mainly used as the conduction path of the instructions (current) issued by the brain. Human nerves have a threshold, which is usually decreased when the nerves get damages. Accordingly, the human body will be susceptible to the pain of the nerve injury portion. If the nerve damage doesn’t have timely and properly treatment, a chronic pain disease of this nerve injury portion will be incurred.

[0003] Electrical stimulation is a common treatment for relieving pain in patients of chronic pain disease. Generally, the patient temporary reliefs of pain after the electrical stimulation treatment, but this comfort can’t last for a long time. Thus, the patient needs frequent electrical stimulation treatments in order to maintain the comfortable state.

[0004] In addition, with the improvement of electrical stimulation technology, the electrical stimulation methods are developed for different symptoms. For example, the spinal nerve electrical stimulation can be used to treat paralysis and the likes. The cerebral cortical electrical stimulation can be used to treat Parkinson's disease. The bladder nerve stimulation can be used to solve the problem that the stroke and paralysis patient can’t spontaneous urination, thereby avoiding the possible complications. The retinal nerve stimulation can help the blind patients to re-feel the weak light and have rough sight. For different applications, the electrical stimulation 1 signals may require different electric fields, voltages, currents, durations and frequencies. 2016250332 24 Oct 2016

SUMMARY

[0005] An aspect of the disclosure is to provide an electrical stimulation device for electrically stimulating at least one target zone of an organism. The electrical stimulation device comprises a control unit and an electrical stimulation unit. The electrical stimulation unit includes a frequency synthesizer, an amplifier, a variable resistor, at least one first electrode and at least one second electrode. The frequency synthesizer is coupled to the control unit and generates a frequency signal. The amplifier is coupled to the frequency synthesizer. The variable resistor comprises a resistance and is coupled to the control unit and the amplifier. The first electrode and the second electrode are coupled to the amplifier. The amplifier outputs an electrical stimulation signal according to the frequency signal of the frequency synthesizer and the resistance of the variable resistor to impel the first electrode and the second electrode to generate an electric field. The electric field covers the target zone, and the electric field strength ranges from 100 V/m to 5000 V/m, so as to electrically stimulate the target zone of the organism.

[0006] In one embodiment, the first electrode and the second electrode are coupled to a mixer. The electrical stimulation signal impels the first electrode and the second electrode to generate an electric field. The electric field covers the target zone, and the electric field strength ranges from 100 V/m to 5000 V/m.

[0007] In one embodiment, the first electrode and the second electrode are coupled to a mixer. The electrical stimulation signal impels the first electrode and the second electrode to generate an electric field. The electric field covers the target zone, and the electric field strength ranges from 100 V/m to 5000 V/m. 2 [0008] In one embodiment, the frequency synthesizer is coupled to an input of the amplifier. 2016250332 24 Oct 2016 [0009] In one embodiment, the variable resistor is coupled to the input of the amplifier.

[0010] In one embodiment, the variable resistor is coupled to an output of the amplifier.

[0011] In one embodiment, the electrical stimulation unit further comprises a wave filter which is coupled between the frequency synthesizer and the amplifier.

[0012] In one embodiment, the electrical stimulation unit further comprises a detector which is coupled to the control unit and the amplifier and detects the electrical stimulation signal.

[0013] In one embodiment, the electrical stimulation unit further comprises a surge protector which is coupled to the amplifier.

[0014] In one embodiment, the electrical stimulation device is an implanted electrical stimulation device.

[0015] In one embodiment, the frequency of the electrical stimulation signal ranges from 200 KHz to 1000 KHz.

[0016] In one embodiment, the voltage of the electrical stimulation signal is bi-phase, and its absolute value is between 3 V and 12V.

[0017] In one embodiment, the second pulse wave signal is substantially a delay signal of the first pulse wave signal.

[0018] In one embodiment, the amplitude of the first wave signal does not equals to that of the second wave signal. 3 [0019] In one embodiment, there is a time difference between the first pulse wave signal and the second pulse wave signal. 2016250332 24 Oct 2016 [0020] An aspect of the disclosure is to provide a method applied to electrically stimulate a target zone of an organism by an implanted electrical stimulation device. The implanted electrical stimulation device comprises a frequency synthesizer, a variable resistor and at least a first electrode and at least a second electrode. The method comprises the following steps. A frequency signal is generated by the frequency synthesizer. An electrical stimulation signal is outputted according to the frequency signal and the resistance of the variable resistor. And, the electrical stimulation signal is delivered by the first electrode and the second electrode to generate an electrical field between the first electrode and the second electrode to electrically stimulate the target zone. The electric field covers the target zone, and the electric field strength ranges from 100 V/m to 5000 V/m.

[0021] In one embodiment, the frequency of the electrical stimulation signal ranges from 200 KHz to 1000 KHz.

[0022] In one embodiment, the method further comprises the following steps. A first pulse wave signal and a second pulse wave signal are generated and a biphasic pulse signal is outputted according to the plurality of first pulse wave signal and the second pulse wave signal. The amplifier outputs the electrical stimulation signal according to the biphasic pulse signal, and the frequency signal and the resistance of the variable resistor. The difference between the integrated value of the amplitude of the first pulse wave signal and the integrated value of the amplitude of the second pulse wave signal versus time is not more than ten percent of the integrated value of the amplitude of the first pulse wave signal versus time [0023] In one embodiment, the second pulse wave signal is substantially a delay 4 signal of the first pulse wave signal. 2016250332 24 Oct 2016 [0024] In one embodiment, the amplitude of the first wave signal does not equals to that of the second wave signal.

[0025] In one embodiment, there is a time difference between the first pulse wave signal and the second pulse wave signal.

[0026] Accordingly, the electrical stimulation device balances the charges through a synthesized signal with staggered positive phases and negative phases, so as to reduce the possibility of damages to the targeted nerve incurred by electrical stimulation signals. The electrical stimulation device can provide electrical stimulation signals with various characteristics to the patient, so as to carry out appropriate electrical stimulation therapy, according to various needs.

BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The embodiments will become more fully understood from the detailed description and accompanying drawings, which are given for illustration only, and thus are not limitative of the present invention, and wherein: [0028] Fig. 1A is a schematic diagram showing the electrical stimulation device applied to the dorsal root ganglion according to the first embodiment; [0029] Fig. IB is a circuit block diagram of the electrical stimulation device and the controller in FIG. 1A; [0030] Figs. 1C and ID are enlarged diagrams showing a lead of the electrical stimulation unit in FIG. 1A; [0031] Figs. 2A and 2B are schematic diagrams showing the electrical stimulation device according to another embodiment; 5 [0032] Fig. 3A is a schematic diagram showing the electrical stimulation device according to one embodiment; 2016250332 24 Oct 2016 [0033] Fig. 3B is a circuit block diagram of the amplifier of the electrical stimulation device according to one embodiment; [0034] Fig. 3C is a schematic diagram showing the waveform of the frequency signal generated by the electrical stimulation device according to one embodiment; [0035] Fig. 4A is a block diagram showing an electrical stimulation device according to another embodiment; [0036] Fig. 4B is a schematic diagram showing the filter of the electrical stimulation device in Fig. 4A; [0037] Fig. 5A is a block diagram showing an electrical stimulation device according to another embodiment; [0038] Fig. 5B is a circuit block diagram showing the differential amplifier of the electrical stimulation device in Fig. 5A; [0039] Fig. 5C is a circuit block diagram showing the amplifier of the electrical stimulation device in Fig. 5A; [0040] Figs. 6A to 6D are schematic diagrams showing the waveforms of the biphasic pulse signals; [0041] Fig. 7 is a schematic diagram showing the electrical stimulation signal according to one embodiment; and [0042] Figs. 8A to 8D are schematic diagrams showing the waveforms of the electrical stimulation signal according to various embodiments. 6

DETAILED DESCRIPTION OF THE INVENTION 2016250332 24 Oct 2016 [0043] The embodiments of the invention will be apparent from the following detailed description, which proceeds with reference to the accompanying drawings, wherein the same references relate to the same elements.

[0044] In order to make the structure of the present device easier to understand in relation to other cooperating devices in practice, the following describes the configuration of the electrical stimulation device for electrical stimulation of the target zone of the organism and the circuit configuration of the controller and the coordination with each other.

[0045] As shown in Fig. 1A, the electrical stimulation device 1 may be provided externally or at least partially implanted within the individual for electrical stimulation therapy, and the electrical stimulation device 1 is preferably a nerve stimulation device, such as a spinal dorsal root ganglion stimulation. The stimulated target region may be, for example, but not limited to, applied to the brain, spinal, and/or spinal dorsal horn, epidural space of an electrically stimulating organism. The above-mentioned spine refers specifically to the ninth thoracic nerve (T9 vertebrae) and the tenth thoracic nerve (T10 vertebrae). An individual is an organism and includes mammals, such as mice, humans, rabbits, cattle, sheep, pigs, monkeys, dogs, cats and the like, preferably humans. The electric stimulation device 1 includes a control unit 11 and an electrical stimulation unit 12, in which the electric stimulation unit 12 of the electrical stimulation device 1 is at least partially implanted into the human body as an example, and the electrode of the electrical stimulation unit 12 (the first electrode El, the second electrode E2) is implanted next to the dorsal root ganglion 3 for electrical stimulation. 7 [0046] Fig. IB is a circuit block diagram of the electrical stimulation device 1 and its associated controller 2. Referring to Fig. IB, the electrical stimulation device 1 performs parameter setting and energy supply through the controller 2. Since the controller 2 does not need to be implanted in the living body, it is also called an external controller. Hereinafter, the correlation between the electric stimulation device 2016250332 24 Oct 2016 1 and the controller 2 will be described.

[0047] The electrical stimulation device 1 comprises a control unit 11 and an electrical stimulation unit 12. The electrical stimulation unit 12 is coupled to the control unit 11; the controller 2 comprises another control unit 21, a human machine interface 22, and a power supply unit 23, wherein the human machine interface 22 is coupled to the control unit 21, and the power supply unit 23 is likewise coupled to the control unit 21 and serves as a power source for the controller 2. The power supply unit 23 may be a battery or a rechargeable battery, or may be a power adapter to connect an external mains to provide power.

[0048] In operation, the user can initialize the system setting value of the controller 2 through the human machine interface 22 of the controller 2, and then input the desired setting parameter to the control unit 21 through the human machine interface 22. The human interface 22 may be, for example, a touch key on a portable electronic device, a touch panel, a physical key, or a combination thereof, and is not limited thereto. The control unit 21 instructs the power supply unit 23 to supply the DC power to the components of the electrical stimulation device 1, in particular the electrical stimulation unit 12, for operation. The control unit 11 and the control unit 21 may be realized by a digital circuit such as an integrated circuit (IC) or an analog circuit, for example, a micro-processor, a microcontroller, A logic gate array (FPGA or CPLD), or an application specific integrated circuit (ASIC). The present embodiment is 8 described by way of a microcontroller (MCU), but the present invention is not limited thereto. 2016250332 24 Oct 2016 [0049] Further, the flowing is to describe the detailed structure of the electrical stimulation unit 12. As shown in Figs. 1A to ID, the electrical stimulation unit 12 includes a flexible lead L that includes at least one first electrode El and at least one second electrode El, and the present embodiment includes a group of electrodes, that is, the first electrode El is a positive electrode and the second electrode E2 is a negative electrode. Of course, the number of electrodes provided on the lead L may be two or more, and may be evenly distributed on the lead L of the electrical stimulation unit 12 or only at the end of the lead L. And the electrode is operated in a bi-phase mode so as to form an electric field between the first electrode El and the second electrode E2, the electric field range covers the target region and the electric field intensity ranges from 100 V/m to 5000 V/m, to the target area for electrical stimulation. In the present embodiment, the material of the first electrode El and the second electrode E2 is a metal such as platinum, silver, gold, or other metal pieces having electrical conductivity. Between the first electrode El and the second electrode E2 is actually a region in which a coaxial wire electrically connected to the electrode is wound into a coil or a wire. More specifically, the first electrode El and the second electrode E2 are disposed on one end of the lead wire L, and the other end of the lead wire L has two contacts as a positive electrode and a negative electrode, and the two contacts are electrically connected or electrically coupled to the control unit 11. The first electrode El and the second electrode E2 are connected to a winding wire, and are connected to a contact by a coil. In addition, the coil L is provided with an insulator I in a coil other than the first electrode El and the second electrode E2 cover. In Fig. 1C, a portion of the region of the wire L between the electrodes is removed 9 and the insulator I is removed to show the dense coil disposed therein. 2016250332 24 Oct 2016 [0050] And the ranges of the individual lengths a of the respective electrodes are set in accordance with practical use requirements, and the electrode length a is in the range of 0.5 to 6 mm, preferably 1 to 4 mm. Wherein the individual length a of the first electrode El and the second electrode E2 refers to a length dimension in the direction of the long axis extending parallel to the wire L of the electrical stimulation unit 12. In this case, the distance b between the first electrode El and the second electrode E2 is 1 to 7 mm, preferably 1 to 4 mm.

[0051] And a distance c between the first electrode El and the second electrode E2 of the wire L and the dorsal root ganglion 3. The distance c is defined as a distance between a midpoint between the adjacent first electrode El and the second electrode E2, The shortest distance of the ganglion. In the present embodiment, the distance c is in the range of 0 to 10 mm, and when the distance c is 0 mm, the middle point between the first electrode El and the second electrode E2 is in the projection direction from the dorsal root nerve Section 3 overlaps one another.

[0052] The electric stimulation device 1 used in the embodiment described above is an active type electric stimulation device in which the control unit 11 and the electric stimulation unit 12 can be co-implanted into the target area of the living body, in other words, the control unit 11 and the electrical stimulation unit 12 are implanted subcutaneously in the organism, or the control unit 11 is integrally molded with the electrical stimulation unit 12 to be implanted subcutaneously in the organism. The controller 2, which is electrically coupled to the outside of the living organism through the control unit 11, receives the parameter signal and the electric energy from the other control unit 21 so that the electric stimulation unit 12 can perform electrical stimulation with respect to the target area of the living body. 10 [0053] It should be noted that the present invention provides the form of an electrical stimulation device which is not limited to the above-mentioned electrical stimulation device 1. In other embodiments, the active electrical stimulator may also be implemented in the form of an electrical stimulation device as in Fig. 2A. The electric stimulation device la of the present embodiment has substantially the same components as the electric stimulation device 1 of the foregoing embodiment, and both the control unit 11a and the electric stimulation unit 12a are implanted in a position (subcutaneous) of the epidermis S of the living body. The control unit 1 la of the electric stimulation device la of the present embodiment is integrated with the flexible circuit board (F) and receives the parameter signal and electric energy from another control unit (not shown) outside the living body, The lead wire La of the electric stimulation unit 12a can be electrically stimulated with respect to the subcutaneous nerve 3a of the living body. The electrical stimulation device la of the present embodiment can reduce the volume of the device implanted into the subcutaneous tissue to reduce the burden on the living body (patient). 2016250332 24 Oct 2016 [0054] Alternatively, the electrical stimulation device of the present invention may be in the form of Fig. 2B. As shown in Fig. 2B, the electrical stimulation device lb of the present embodiment is a passive electrical stimulation device which is different from the electrical stimulation device 1 of the foregoing embodiment in that the control unit 1 lb of the electrical stimulation device lb is integrated into the electric stimulation device 1 disposed in the living body epidermis S outside the skin. The implanted electrical stimulation device lb does not have a control unit. While the tail of the electrical stimulation unit lib has a flexible circuit board and is located subcutaneously (e.g., less than 5 cm in depth) deep enough to transmit an electrical stimulation signal to the lead L2 through an external controller 2b that is not 11 implanted in the skin, so that the electrical stimulation unit 12b can perform passive electrical stimulation with respect to the subcutaneous nerve 3a of the living body. 2016250332 24 Oct 2016 [0055] As shown in Fig. 3A, which is a schematic block diagram of a preferred embodiment of the electrical stimulation device of the present invention. The electrical stimulation device 1 includes a control unit 11 and an electrical stimulation unit 12. The control unit 11 may store electrical stimulation parameters and electrical stimulation data and act upon the data-controlled electrical stimulation unit 12 in accordance with these parameters. The electrical stimulation unit 12 includes a pulse wave generator 120, a frequency synthesizer 121, an amplifier 122, and a variable resistor 123. The electrical stimulation unit 12 may receive an instruction from the control unit 11 to output the electrical stimulation signal SI to the subject for electrical stimulation therapy, wherein the voltage of the electrical stimulation signal SI is biphasic to reduce the risk to the nerve of the electrical stimulation therapy and its absolute value ranges from 3 V to 12 V, for example, an alternating current with an amplitude ranging from 3 V to 12 V. Further, the frequency synthesizer 121 is coupled to the control unit 11 and generates a frequency signal S2 whose frequency is greater than 100 kHz in accordance with the control of the control unit 11. In this embodiment, the frequency synthesizer 121 is a direct digital synthesizer as an example. For example, the direct digital synthesizer can be selected from Analog Devices, Inc.'s AD9833, which can output sine, square, or triangular waves with a maximum output frequency of 12.5 MHz and an output voltage of approximately 650 mV, That is, the voltage of the frequency signal S2 of this embodiment is 650 mV. Of course, the present invention does not limit the type of the frequency synthesizer 121, so long as the frequency synthesizer 121 can generate the high-frequency frequency signal S2 and output the high-frequency electrical stimulation signal SI. However, in 12 another embodiment, the frequency synthesizer 121 may also be independently integrated into the control unit 11 (not shown), i.e., the electrical stimulation unit 12 includes only the pulse wave generator 120, the amplifier 122, and the variable A resistor 123. 2016250332 24 Oct 2016 [0056] It should be noted that the electrical stimulation device of the present invention can be driven by current/voltage. For the sake of convenience of explanation, the following paragraphs describe voltage driving as an embodiment. However, in the same circuit architecture, the amplifier 122 may also convert the voltage signal into a current signal to cause the inventive electrical stimulation device to be changed to a current drive. The present invention is not limited thereto.

[0057] Please also refer to Fig. 3B, which is a circuit diagram of the amplifier. In the present embodiment, the amplifier 122 is coupled to a frequency synthesizer 121, which is an operational amplifier (OPA) having an inverting input terminal Ini, a non-inverting input terminal In2, and an output terminal Out. The frequency synthesizer 121 is coupled to one of the inputs (inverting input Ini or non-inverting input In2) of the amplifier 122, wherein the present embodiment is coupled to the inverting input Ini by the frequency synthesizer 121. The input Inl2 is grounded as an example. In this way, since the output voltage of the frequency synthesizer 121 is low (about 650 mV), the present embodiment amplifies the voltage of the frequency signal S2 output from the frequency synthesizer 121 to 3 V to 12 V by the amplifier 122 so as to conform to the above-mentioned voltage set of the signal SI.

[0058] The variable resistor 123 may be a digital potentiometer (digiPOT), and has a resistance value, and is coupled to the control unit 11 and the amplifier 122. For example, the variable resistor 123 is selected from Analog Devices, Inc. AD5290, 10kQ digital variable resistor. The control unit 11 adjusts the resistance value of the 13 variable resistor 123 in accordance with the electric stimulation parameter, so that the resistance value is not a fixed value. Thus, the amplifier 122 outputs the electrical stimulation signal SI according to the frequency signal S2 of the frequency synthesizer 121 and the resistance value of the variable resistor 123. The frequency of the electrical stimulation signal SI is determined by the frequency signal S2 of the frequency synthesizer 121, for example, greater than 100 kHz, such as 200 kHz to 1000 kHz, and the voltage of the electrical stimulation signal SI is determined by the amount of gain of the amplifier 122, where the resistance value of the variable resistor 123 affects the gain of the amplifier 122. It is to be noted that the frequency signal S2 is preferably in the range of 200 kHz to 250 kHz, 250 kHz to 350 kHz, 350 kHz to 450 kHz, 450 kHz to 550 kHz, 550 kHz to 650 kHz, 650 kHz to 750 kHz, 750 kHz to 800 kHz, or 800 kHz to 1000 kHz. When the frequency range is between 200KHz and 450KHz, it can be operated at lower frequency. Thus, the risk of bio-heat is low, and it has the advantage of safety. On the contrary, when the frequency range is 550 kHz -1000 kHz, the resulting electric field density is large, and its electric stimulation effect is better. 2016250332 24 Oct 2016 [0059] Further, in the present embodiment, one end of the variable resistor 123 is coupled to the inverting input terminal Ini of the amplifier 122 and the other end is coupled to the output terminal Out of the amplifier 122. That is, the variable resistor 123 and the amplifier 122 form a negative feedback configuration. The amount of gain of the amplifier 122 is adjusted in accordance with the change in the resistance value of the variable resistor 123, while the control unit 11 adjusts the resistance value of the variable resistor 123 in accordance with the electric stimulation parameter or setting and thereby changes the gain of the amplifier 122 so that the voltage of the stimulation signal SI may be within a pre-set voltage range. 14 [0060] Please also refer to Figure 3C, which is a waveform diagram of the frequency signal. In the present embodiment, the frequency signal S2 is a continuous square wave which is emitted in an intermittent manner. That is, a square wave signal of a high frequency is emitted for a period of time TD (hereinafter referred to as a pulse wave width TD). It is noted that the frequency of the high-frequency square wave signal in Fig. 3C is only indicative, and the actual case frequency should be higher. The high frequency square wave signal has a pulse frequency between 0 and 1 KHz, and in a preferred embodiment, the high frequency square wave signal may have a pulse frequency between 1 and 100 Hz. In the present embodiment, the square wave signal of the high frequency has a pulse frequency of 2 Hz. In addition, the pulse wave width TD (duration) is between 1 and 250 ms. In a preferred embodiment, the pulse wave width TD may be between 10 and 100 ms. In the present embodiment, the pulse width TD is 25 ms. 2016250332 24 Oct 2016 [0061] It is also noted that, in order to prevent the patient from feeling discomfort due to sudden electrical stimulation, in another embodiment, a voltage-driven electrical stimulation device, for example, at the beginning of treatment, is opened by a medical staff or user to activate the electrical stimulation device power supply. The medical staff or the user can manually turn the knob, or the electric stimulation device itself can control the way to make the electrical stimulation signal SI voltage at the beginning of the generation, from 0V to the target voltage value (target voltage The absolute value of the range can be between 3 V and 12V), and can control the speed of the electrical stimulation signal SI voltage boost not to exceed IV per second. For a current-driven electrical stimulation device, the current can slowly increase from 0 mA to the target current at the beginning of treatment (the absolute value of the target current range can be between 0.5 uA and 50 mA) and can be controlled the rate of 15 current stimulation of the electrical stimulation signal SI to not exceed 5 mA per second (preferably not more than 1 mA per second). When the electrical stimulation signal SI is to be turned off after the end of the treatment, it is not necessary to perform a relative current or voltage ramp-down step (the absolute value of the current or voltage is gradually reduced). In a preferred embodiment, the target current value is 25 mA. 2016250332 24 Oct 2016 [0062] Please refer to Figs. 4A and 4B, wherein FIG. 4A is a block diagram of another electrical stimulation device of the present invention, and FIG. 4B is a schematic view of the filter shown in FIG. 4A. In the present embodiment, the electrical stimulation unit 12a further includes a filter 124a coupled between the frequency synthesizer 121 and the amplifier 122. In other words, the filter 124a is coupled to the inverting input terminal Ini. The filter 124a of the present embodiment is a low-pass filter with a cutoff frequency of 1000 kHz to filter out the high frequency portion of the frequency signal S2 so that the signal input to the amplifier 122 is 1000 kHz or less, to match the default frequency range of the electrical stimulation signal SI (100 kHz to 1000 kHz). As shown in Fig. 4B, the filter 124a can be realized by coupling the capacitor C and the complex resistance R by another amplifier A. Herein, the second-order low-pass filter is taken as an example, but is not intended to limit the present invention.

[0063] Please refer to Fig. 3A. It should be noted that the electric power source of the electrical stimulation device 1 may also be a built-in battery that is coupled to a power management unit (not shown) and the power management unit may provide power to the battery to the control unit 11 and the electrical stimulation unit 12. Alternatively, the power source may be an external power supply unit, such as a wireless charging unit having a coil and a rectifier that couples a magnetic field 16 generated by the wireless power supply device by a coil to produce an induced current and the rectifier rectifies the induced current to a DC current to the power management unit of the electrical stimulation device 1 to supply to the control unit 11 and the electrical stimulation unit 12. In addition, the power management unit may include a voltage invertor that reverses the polarity of the received voltage to provide the reverse operating voltage required by the amplifier 122. 2016250332 24 Oct 2016 [0064] Referring again to FIG. 4A, the electrical stimulation unit 12a may further include a detector 125 coupled to the control unit 11 and the amplifier 122 and detecting the electrical stimulation signal SI. In the present embodiment, the detector 125 is an output terminal Out coupled to the amplifier 122, and the control unit 11 may detect the voltage of the electrical stimulation signal SI, for example, whether or not the waveform of the output Out is matched with a preset waveform (for example, 3V to 12V described above). The control unit 11 may modify the electrical stimulation parameter in real time, for example, by changing the resistance value of the variable resistor 123 such that the electrical stimulation signal SI conforms to the electrical stimulation signal SI when the waveform of the electrical stimulation signal SI deviates from the preset waveform (such as 3V to 12V described above). For example, changing the resistance value of the variable resistor 123, so that the electrical stimulation signal SI conforms to the aforementioned voltage range, and thus to avoid outputting an electrical stimulation signal SI with erroneous voltage.

[0065] In addition, in some embodiments, the electrical stimulation unit 12a may further include a surge protection 126 that couples the amplifier 122, for example, to the output End Out of the coupling amplifier 122. In one embodiment, the surge protector 126 may be, for example, a zener diode, a transient duration suppression (TVS) diode, or a bidirectional ESD protection diodes. International Organization for 17

Standardization International Standard No. ISO 14708-3 stipulates that active implantable medical devices (AIMDs) implanted in an individual are not to be used in a patient (such as a patient) to produce a permanent influences. Thus, the provision of the surge protector 126 may limit the high voltage (e.g., 1000 V) pulses provided by the defibrillator to a low voltage acceptable to the human body, such as 5 V, to prevent nerve damage due to the high voltage pulse and avoid the electrical stimulation unit 12a in the abnormal output voltage of the electrical stimulation signal SI, and cause damage to the individual. 2016250332 24 Oct 2016 [0066] In addition, in other embodiments, one end of the variable resistor 123 may couple only the input terminal, while the other end receives the frequency signal S2. The control unit 11 can change the voltage of the frequency signal S2 in a voltage-dividing manner by changing the resistance value of the variable resistor 123, thereby changing the voltage of the electrical stimulation signal SI outputted from the amplifier 122.

[0067] In addition, in some embodiments, one end of the variable resistor 123 may be coupled only to the output Out and the other end to the ground, so that the control unit 11 can also vary the voltage by varying the resistance of the variable resistor 123, The voltage of the stimulation signal SI.

[0068] In general, the neurons of the central nervous system mainly consist of sensory neurons and motor neurons, in which the high frequency electrical stimulation signal does not affect the sensory neurons or the sensory neurons. High-frequency electrical stimulation of the sensory neurons or motor neurons will not stimulate. That is, the human body is not feeling. Thus, when a patient is treated with a high frequency electrical stimulation signal, it may occur that the patient has no psychological effect on the treatment because no electrical stimulation is sensed. In 18 order to solve this problem, in the course of treatment, can add some low-frequency electrical stimulation signal to make the patient feel the treatment process, and thus more peace of mind to accept treatment. In addition, by low frequency electrical stimulation signals, it is also possible to position the electrodes or devices of the medical personnel during the implantation of the electrical stimulation device, so as to prevent the user from not finding the offset of the position of the electrical stimulation device until implantation complete. 2016250332 24 Oct 2016 [0069] Fig. 5A is a schematic block diagram of another embodiment of the electrical stimulation device of the present invention, and FIG. 5B is a circuit diagram of a differential amplifier of the electrical stimulation device of FIG. 5 A. FIG. 5C is a circuit diagram of the amplifier of the electrical stimulation device of FIG. 5 A. The structure of the electrical stimulation device lb is substantially the same as that of the electrical stimulation device la, except that the electric stimulation unit 12b of the electrical stimulation device lb further includes a pulse wave generator 120 and a differential amplifier 124. The amplifier 122b of the stimulation device lb is a summing amplifier. The pulse wave generator 120 generates a set of pulse wave signals, respectively, and generates the biphasic pulse wave signal S3 after the differential amplifier 124 is added. Since the biphasic pulse wave signal S3 is essentially a low-frequency signal, it is possible to cause the patient to feel sensory (via sensory neurons) or cause muscle contraction (via motor neurons) after adding the electrical stimulation signal SI to the amplifier 122b. In the biphasic pulse signal S3, the charge balance is required between the positive phase signal portion and the negative phase signal portion in order to reduce the harm to nerve caused by the electrical stimulation therapy. In the present invention, the charge balance is defined as "the absolute value of the sum of the integrated value obtained by integrating the 19 positive-phase signal portion with respect to time and the integrated value obtained by integrating the negative-phase signal portion with respect to time is not larger than one-tenth of the integrated value obtained by integrating the positive-phase signal portion with respect to time.” 2016250332 24 Oct 2016 [0070] Please refer to Figs. 5A and 5B. Fig. 5B is a circuit diagram of a preferred embodiment of the differential amplifier 124 of the electrical stimulation device of the present invention. The differential amplifier 124 is an operational amplifier (OPA) having an inverting input terminal Ini, a non-inverting input terminal In2, and an output terminal Out. The pulse wave generator 120 generates the first pulse wave signal SP1 and at least one second pulse wave signal SP21 to SP2 4. In the present embodiment, the first pulse signal SP1 of the pulse wave generator 120 is coupled to the non-inverting input terminal In2 of the differential amplifier 124 through a resistor Rl, and the non-inverting input terminal In2 of the differential amplifier 124 is coupled to ground through a resistor R2. A resistor R3 is coupled between the output terminal of the differential amplifier 124 and the non-inverting input terminal In2. The second pulse signals SP21 to SP2 4 of the pulse wave generator 120 are respectively coupled to the inverting input terminal Ini of the differential amplifier 124 through resistors R4 to R7. As a result, the biphasic pulse signal S3 can be calculated by the following formula: S3=SP1· (R2/ (R1+R2) ) · (R3/ (R4//R5//R6//R7) ) +SP2_1 (-R3/R4) +SP2_2 (-R3/R5) +SP2 3 (-R3/R6) +SP2_4 (-R3/R7) [0071] In the present embodiment, R1=R2=R3 , R4=R5=8*R1, R6=4*R1, R7=2*R1. Therefore, the above equation becomes: S3 = SP1+SP2 1· (-1/8) +SP2 2· (-1/8) + SP2 3· (-2/8) +SP2 3· (-4/8) 20 [0072] As can be seen from the above equation, the positive phase signal portion of the biphasic pulse wave signal S3 is constituted by the first pulse wave signal SP1, and the negative phase signal portion is constituted by the second pulse wave signals SP21 to SP2 4. As a result, the electrical stimulation apparatus of the present invention can adjust the waveform of the negative-phase signal portion by controlling the second pulse wave signals SP21 to SP2 4. 2016250332 24 Oct 2016 [0073] For example, reference is made to Figures 6A to 6D, which are waveform diagrams of a preferred embodiment of a biphasic pulse wave signal. In Fig. 6A, the first pulse signal SP1 has an amplitude Ap and a wave width Tp; the second pulse wave signals SP21 to SP2 4 have an amplitude An and a wave width Tn. In the present embodiment, the amplitude Ap is equal to the amplitude An and is between 3 V and 12 V, the width Tp is equal to the width Tn, and is between 50 ps and 100 ps. As a result, the second pulse signal SP21 passes through the differential amplifier 124 and becomes inverted, and the amplitude becomes 1/8 · Ap. The second pulse signal SP2 2 passes through the differential amplifier 124 and becomes inverting and the amplitude becomes 1/8 · Ap. The second pulse signal SP2 3 passes through the differential amplifier 124 and becomes inverting, and the amplitude becomes 1/4 · Ap. The second pulse signal SP2 4 passes through the differential amplifier 124 and becomes inverting, and the amplitude becomes 1/2 · Ap. After the second pulse signals SP21 to SP_4 are added via the differential amplifier 124, the amplitude is just equal to Ap and becomes opposite to the first pulse signal SP1.

[0074] In Fig. 6B, the first pulse signal SP1 has an amplitude Ap and a wave width Tp; the second pulse wave signals SP21 to SP2 3 have an amplitude An and a wave width Tn. In this embodiment, the amplitude Ap is equal to the amplitude An, and between 3 V and 12 V, and the wave width Tn is equal to twice the wave width Tp, 21 and is between 50 ps and 100 ps, in order to achieve charge balance. As a result, the second pulse signal SP2_1 passes through the differential amplifier 124 and becomes inverted, and the amplitude becomes 1/8 · Ap. The second pulse signal SP2_2 passes through the differential amplifier 124 and becomes inverted and the amplitude becomes 1/8 · Ap. The second pulse signal SP2 3 passes through the differential amplifier 124 and becomes inverted, and the amplitude becomes 1/4 · Ap. After the second pulse signal SP2_1 to SP_4 is added via the differential amplifier 124, the amplitude is exactly equal to 1/2 · Ap, and becomes opposite to the first pulse signal SP1. Since the wave width Tn is equal to twice the wave width Tp, the charge balance is still satisfied. 2016250332 24 Oct 2016 [0075] In Fig. 6C, the first pulse signal SP1 has an amplitude Ap and a wave width Tp; the second pulse wave signals SP2_1 to SP2_4 have an amplitude An and a wave width Tn. In the present embodiment, the amplitude Ap is equal to the amplitude An, the width Tp is equal to the width Tn, and the first pulse wave signal SP1 and the second pulse wave signals SP21 to SP2 4 have a time difference Td. As a result, the second pulse signal SP21 passes through the differential amplifier 124 and becomes inverted, and the amplitude becomes 1/8 · Ap. The second pulse signal SP2 2 passes through the differential amplifier 124 and becomes inverted and the amplitude becomes 1/8 · Ap. The second pulse signal SP2 3 passes through the differential amplifier 124 and becomes inverted, and the amplitude becomes 1/4 · Ap. The second pulse signal SP2 4 passes through the differential amplifier 124 and becomes inverted, and the amplitude becomes 1/2 · Ap. After the second pulse signals SP21 to SP_4 are added via the differential amplifier 124, the amplitude is just equal to Ap and becomes opposite to the first pulse signal SP1.

[0076] It is noted that, in another embodiment, the capacitor C (not shown) may be 22 connected in series with the resistor R3. This allows the negative phase signal portion of the biphasic pulse wave signal S3 to be attenuated (as shown in Fig. 6D) so that the biphasic pulse signal S3 is applied to a patient of a different constitution. 2016250332 24 Oct 2016 [0077] Please refer to Fig. 5C. In the present embodiment, the amplifier 122b is a summing amplifier coupled to the differential amplifier 124, the variable resistor 123, and the frequency synthesizer 121. The amplifier 122b is an operational amplifier (OPA) having an inverting input terminal Ini, a non-inverting input terminal In2, and an output terminal Out. The output of the frequency synthesizer 121 is coupled to one of the inputs (inverting input Ini or inverting input In2) of the amplifier 122b and the output of the differential amplifier 124 is also coupled to the same input of the amplifier 122b. The present embodiment is described by taking the frequency synthesizer 121 coupled to the inverting input terminal Ini and the noninverting input terminal In 12 connected to ground as an example. In this way, since the output voltage of the frequency synthesizer 121 is low (about 650 mV), the present embodiment amplifies the voltage of the frequency signal S2 outputted from the frequency synthesizer 121 to 3 V to 12 V by the amplifier 122b so as to conform to the voltage setting of the electrical stimulation signal SI. The amplifier 122b adds the frequency signal S2 and the biphasic pulse wave signal S3 (for example, in Fig. 6B) to obtain the electrical stimulation signal SI whose waveform is as shown in Fig. 7.

[0078] It is noted that the time difference between the biphasic pulse wave signal S3 and the frequency signal S2 needs to be maintained for at least 2 micro-seconds. In addition, the biphasic pulse wave signal S3 may be designed to be issued at least once before and/or after the course of treatment to indicate the beginning and/or the end of the patient, during the electrical stimulation therapy. The biphasic pulse wave signal S3 may also be designed as an intermittent periodic signal in another design variation, 23 such as when the electrical stimulation device is implanted. For example, the pulse wave generator 120 may control the generation of the pulse wave signals SP1, SP21 to SP2 4 such that the differential amplifier intermittently generates four biphasic pulse wave signals S3 in the four pulse wave periods TP of the frequency signal S2. Each biphasic pulse signal S3 has a duration Tm and is spaced at least 2 micro-seconds. Thus, the electrical stimulation signal SI, which is synthesized by the frequency signal S2 and the biphasic pulse wave signal S3 transmitted through the amplifier 122b, is as shown in Figs. 8A to 8D. Figs. 8A to 8D are waveform diagrams in different embodiments of the electrical stimulation signal of the present invention. Figs. 8A to 8D are merely illustrative of the possible waveforms of the electrical stimulation signal SI synthesized by the frequency signal S2 and the biphasic pulse wave signal S3. The waveform of the electrical stimulation signal SI may also have other variations. As long as the pulse wave generator 120 controls the occurrence of the biphasic pulse wave signal S3 at a frequency no greater than the pulse wave frequency of the frequency signal S2, the waveform of the finally generated electrical stimulation signal SI is within the scope of the present invention. 2016250332 24 Oct 2016 [0079] In summary, the electric stimulation apparatus of the present invention adjusts the frequency of the output signal by the frequency synthesizer and adjusts the voltage range of the output signal through the amplifier and the variable resistor so that the first electrode and the second electrode generate electric field strengths of 100 V/m to 5000 V/m. In this way, the electrical stimulation device can provide the electric stimulation signal of the different electric field strength to the patient according to the different application way and give the appropriate electrical stimulation treatment to the patient. In another aspect, the electrical stimulation apparatus of the present invention adds a pulse wave of the same total amount of 24 charge to a bi-directional pulse wave of charge balance by a pulse wave generator and a differential amplifier, so as to avoid the harm to nerve caused by the electrical stimulation signal. 2016250332 24 Oct 2016 [0080] Although the invention has been described with reference to specific embodiments, this description is not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternative embodiments, will be apparent to persons skilled in the art. It is, therefore, contemplated that the appended claims will cover all modifications that fall within the true scope of the invention. 25

Claims

CLAIMS What is claimed is:

1. An electrical stimulation device for electrically stimulating at least one target zone of an organism, comprising a control unit; and an electrical stimulation unit including: a frequency synthesizer which is coupled to the control unit and generates a frequency signal; an amplifier which is coupled to the frequency synthesizer; a variable resistor which comprises a resistance and is coupled to the control unit and the amplifier; and at least one first electrode and at least one second electrode, wherein the first electrode and the second electrode are coupled to the amplifier, wherein the amplifier outputs an electrical stimulation signal according to the frequency signal of the frequency synthesizer and the resistance of the variable resistor to impel the first electrode and the second electrode to generate an electric field, the electric field covers the target zone, and the electric field strength ranges from 100 V/m to 5000 V/m.
2. The electrical stimulation device according to claim 1, wherein the frequency synthesizer is coupled to an input of the amplifier.
3. The electrical stimulation device according to claim 2, wherein the variable resistor is coupled to the input of the amplifier.
4. The electrical stimulation device according to claim 2, wherein the variable resistor is coupled to an output of the amplifier.
5. The electrical stimulation device according to claim 3, wherein the variable resistor is coupled to an output of the amplifier.
6. The electrical stimulation device according to claim 1, wherein the electrical stimulation unit further comprises a wave filter which is coupled between the frequency synthesizer and the amplifier.
7. The electrical stimulation device according to claim 1, wherein the electrical stimulation unit further comprises a detector which is coupled to the control unit and the amplifier and detects the electrical stimulation signal.
8. The electrical stimulation device according to claim 1, wherein the electrical stimulation unit further comprises a surge protector which is coupled to the amplifier.
9. The electrical stimulation device according to claim 1, wherein the electrical stimulation device is an implanted electrical stimulation device.
10. The electrical stimulation device according to claim 1, wherein the frequency of the electrical stimulation signal ranges from 200 KHz to 1000 KHz.
11. The electrical stimulation device according to claim 1, wherein the voltage of the electrical stimulation signal is bi-phase, and its absolute value is between 3 V and 12 V.
12. The electrical stimulation device according to claim 1, wherein the amplifier is a summing amplifier, and the electrical stimulation device further comprises: a pulse wave generator which is coupled to the control unit and generate a plurality of pulse signals; and a differential amplifier which is coupled to the pulse wave generator and the amplifier, and outputs a biphasic pulse signal according to the plurality of pulse signals, wherein the amplifier outputs the electrical stimulation signal according to the biphasic pulse signal, the frequency signal and the resistance of the variable resistor.
13. The electrical stimulation device according to claim 11, wherein the biphasic pulse signal comprises a positive-phase signal part a negative-phase signal part, and the absolute value of the sum of the integrated value of the positive-phase signal part with respect to time and the integrated value of the negative-phase signal part with respect to time is not more than one tenth of the integrated value of the positive-phase signal part with respect to time.
14. A method applied to electrically stimulate a target zone of an organism by an implanted electrical stimulation device, wherein the implanted electrical stimulation device comprises a frequency synthesizer, a variable resistor and at least a first electrode and at least a second electrode, the method comprising: generating a frequency signal by the frequency synthesizer; outputting an electrical stimulation signal according to the frequency signal and the resistance of the variable resistor, and delivering the electrical stimulation signal by the first electrode and the second electrode to generate an electrical field between the first electrode and the second electrode to electrically stimulate the target zone, wherein the electric field covers the target zone, and the electric field strength ranges from 100 V/m to 5000 V/m.
15. The method according to claim 13, wherein the frequency of the electrical stimulation signal ranges from 200 KHz to 1000 KHz.
16. The method according to claim 13, wherein the method further comprises: generating a plurality of pulse signals; and outputting a biphasic pulse signal according to the plurality of pulse signals, outputting the electrical stimulation signal according to the biphasic pulse signal, and the frequency signal.
17. The method according to claim 13, wherein the biphasic pulse signal comprises a positive-phase signal part a negative-phase signal part, and the absolute value of the sum of the integrated value of the positive-phase signal part with respect to time and the integrated value of the negative-phase signal part with respect to time is not more than one tenth of the integrated value of the positive-phase signal part with respect to time.