WO2018059568A1 - 用于神经刺激的脉冲电流产生电路、电荷补偿电路和方法及植入式视网膜电刺激器 - Google Patents

用于神经刺激的脉冲电流产生电路、电荷补偿电路和方法及植入式视网膜电刺激器 Download PDF

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Publication number
WO2018059568A1
WO2018059568A1 PCT/CN2017/104678 CN2017104678W WO2018059568A1 WO 2018059568 A1 WO2018059568 A1 WO 2018059568A1 CN 2017104678 W CN2017104678 W CN 2017104678W WO 2018059568 A1 WO2018059568 A1 WO 2018059568A1
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Prior art keywords
pulse current
charge
circuit
signal
pulse
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PCT/CN2017/104678
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English (en)
French (fr)
Inventor
夏斌
赵瑜
林郁
方贤文
陈志�
Original Assignee
深圳硅基仿生科技有限公司
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Priority claimed from CN201610879293.4A external-priority patent/CN106267560B/zh
Priority claimed from CN201610875326.8A external-priority patent/CN106390285B/zh
Application filed by 深圳硅基仿生科技有限公司 filed Critical 深圳硅基仿生科技有限公司
Priority to US16/337,920 priority Critical patent/US11097105B2/en
Publication of WO2018059568A1 publication Critical patent/WO2018059568A1/zh
Priority to US17/445,215 priority patent/US12076551B2/en
Priority to US17/445,214 priority patent/US11998741B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36046—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation of the eye
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36142—Control systems for improving safety
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36146—Control systems specified by the stimulation parameters
    • A61N1/36167—Timing, e.g. stimulation onset
    • A61N1/36175—Pulse width or duty cycle
    • H—ELECTRICITY
    • H03—ELECTRONIC CIRCUITRY
    • H03K—PULSE TECHNIQUE
    • H03K3/00—Circuits for generating electric pulses; Monostable, bistable or multistable circuits
    • H03K3/01—Details
    • H03K3/017—Adjustment of width or dutycycle of pulses
    • H—ELECTRICITY
    • H03—ELECTRONIC CIRCUITRY
    • H03K—PULSE TECHNIQUE
    • H03K3/00—Circuits for generating electric pulses; Monostable, bistable or multistable circuits
    • H03K3/78—Generating a single train of pulses having a predetermined pattern, e.g. a predetermined number
    • H—ELECTRICITY
    • H03—ELECTRONIC CIRCUITRY
    • H03K—PULSE TECHNIQUE
    • H03K5/00—Manipulating of pulses not covered by one of the other main groups of this subclass
    • H03K5/00006—Changing the frequency
    • H—ELECTRICITY
    • H03—ELECTRONIC CIRCUITRY
    • H03K—PULSE TECHNIQUE
    • H03K5/00—Manipulating of pulses not covered by one of the other main groups of this subclass
    • H03K5/01—Shaping pulses
    • H03K5/02—Shaping pulses by amplifying
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526—Head electrodes
    • A61N1/0543—Retinal electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36125—Details of circuitry or electric components
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36146—Control systems specified by the stimulation parameters
    • A61N1/3615—Intensity
    • A61N1/36157—Current

Definitions

  • the present invention relates to a pulse current generating circuit for nerve stimulation, a charge compensation circuit and method, and an implantable retinal electrical stimulator.
  • RP retinitis pigmentosa
  • AMD macular degeneration
  • an external camera captures a video image, and then the image processing device converts the video image into an electrical signal and sends it to the implant, and then the implant located in the eye converts the electrical signal into a stimulus signal and passes
  • the stimulating electrode of the implant stimulates the ganglion cells of the retina, thereby enabling the blind to feel the light perception on the cerebral cortex and restore part of the vision.
  • the stimulation signals generated by the stimulation electrodes often only stimulate nerve cells (such as ganglion cells) on the surface of the retina, and cannot effectively It stimulates the bipolar cells of the retina slightly away from the surface of the retina. Therefore, it is often not ideal in terms of stimulating effect.
  • nerve cells such as ganglion cells
  • stimulated nerve tissue such as ganglion cells or bipolar cells of the retina
  • a net charge such as positive or negative charge
  • the RC circuit In order to ensure the balance of the stimulating charge received by nerve tissue such as ganglion cells or bipolar cells of the retina, it is also considered to provide an RC circuit between the pulse current generating circuit and the stimulated site to balance the ganglion cells or bipolar cells. Excess charge. However, the charge balance performance of the RC circuit is positively correlated with the capacity of the capacitor in the RC circuit. In order to balance more positive or negative charges, the capacity of the capacitor in the RC circuit needs to be increased, thereby requiring a larger area of capacitance. However, in the field of neural stimulation, the circuit design space is often limited, and the integrated area cannot occupy a large capacitance. Therefore, the use of the RC circuit to balance the charge capacity cannot be fully utilized.
  • the inventors of the present invention have found through long-term studies that ganglion cells are connected to a plurality of bipolar cells in the retina, and bipolar cells and single photoreceptor cells are in the macular area of the retina (usually the implantation site of the artificial retina). Corresponding connections, by stimulating the bipolar cells of the retina, can effectively improve the resolution of the stimulus, resulting in a more accurate and effective light perception.
  • the stimulating electrode implanted in the body often fits on the retina, and the part that the stimulating electrode can contact is mainly the ganglion cells of the retina (especially ganglion cells). Axon).
  • the stimulation electrode In order for the stimulation signal generated by the stimulation electrode to be stimulated to bipolar cells that are slightly distant from the stimulation electrode, it is generally required that the stimulation electrode be capable of providing a pulse current such as a wide stimulation pulse. In addition, from the viewpoint of the safe charge amount of the stimulating electrode, if the stimulation pulse of the pulse current is wide, the amplitude of the pulse current is correspondingly reduced to ensure that the stimulating charge is within the range of the safe charge amount.
  • an object of the present invention is to provide a pulse current generating circuit, a charge compensation circuit and method, and an implantable retinal electrical stimulator for nerve stimulation capable of improving effective stimulation resolution.
  • a first aspect of the present invention provides a pulse current generating circuit for nerve stimulation, comprising: an analog signal receiving device for receiving an analog signal; and an analog to digital converter that converts the analog signal into a digital a control signal; a current signal controller that generates a pulse current parameter for generating a bidirectional pulse current signal based on the digital control signal; and a current generator that generates the bidirectional pulse for nerve stimulation based on the pulse current parameter a current signal capable of generating a current based on the pulse current parameter The same precision pulse current.
  • the current signal controller generates a pulse current parameter for generating a bidirectional pulse current signal according to the digital control signal
  • the current generator generates a bidirectional pulse current for nerve stimulation of different precision according to the pulse current parameter. signal.
  • the total amount of charges of the bidirectional pulse current signal is within a safe charge amount in one stimulation period. Therefore, it is possible to prevent the pulse current signal from injuring human nerve tissue (for example, ganglion cells or bipolar cells of the retina), and ensuring the safety and reliability of the pulse current generating circuit.
  • human nerve tissue for example, ganglion cells or bipolar cells of the retina
  • the pulse current parameter includes a negative pulse width, a negative pulse amplitude, a forward pulse width, a forward pulse amplitude, and a pulse interval.
  • the current generator generates a low-precision pulse current or a high-precision pulse current according to the pulse current parameter, and the current generator receives the pulse After the current parameter, determining whether the bidirectional pulse current signal to be generated is less than a critical value, and generating the high precision pulse current when the bidirectional pulse current signal to be generated is less than or equal to a critical value; when the bidirectional pulse current signal to be generated is greater than At the critical value, the low precision pulse current is generated.
  • the current generator can generate a corresponding pulse current under different conditions to meet the requirements of the stimulation signal.
  • the current generator when the negative pulse width of the bidirectional pulse current signal is greater than the preset duration and the negative pulse amplitude is less than or equal to the At the critical value, the current generator generates a high precision pulse current. In this case, nerve cells are stimulated more effectively.
  • the accuracy of the pulse amplitude of the high-precision pulse current is greater than the precision of the pulse amplitude of the low-precision pulse current.
  • the current generator can generate pulse currents of different precision according to actual conditions to meet the requirements of different nerve stimulation signals.
  • the total amount of charges of the forward pulse current or the negative direction pulse current in one stimulation period of the bidirectional pulse current signal is within the safe charge amount. Therefore, long-term safety and reliability of the stimulating electrode can be ensured.
  • a second aspect of the present invention provides a charge compensation circuit which is a charge compensation circuit for performing charge compensation on a pulse current generation circuit, the pulse current generation circuit generating a bidirectional pulse current for nerve stimulation
  • the charge compensation circuit includes: a detection circuit for detecting a total amount of charges in one stimulation period of the bidirectional pulse current signal generated by the pulse current generation circuit; and a determination circuit for determining that the detection circuit detects Whether the total amount of charge exceeds a safe charge amount; and a compensation circuit for generating a compensated pulse current signal having a net charge amount when the determination circuit determines that the total amount of charge exceeds a safe charge amount The total amount of charge is within the safe charge amount.
  • the total amount of electric charge of the bidirectional pulse current signal generated by the pulse current generating circuit in one stimulation period is detected by the detecting circuit, and the judging circuit is used to determine whether the total amount of electric charge detected by the detecting circuit is The safe charge amount is exceeded, and when the judging circuit judges that the total amount of charge exceeds the safe charge amount, the compensation circuit generates a compensated pulse current signal having a net charge amount such that the total amount of charge is within the safe charge amount.
  • RC circuit a large capacitance
  • the compensation circuit when the determination circuit determines that the total amount of charge is a positive value, a compensation pulse current signal having a negative compensation amount of charge is generated. Making the total amount of charge within the safe charge amount, and when the determining circuit determines that the total amount of charge is a negative value, generating a compensated pulse current signal having a positive value of the compensated charge amount to make the total charge The amount is within the safe charge amount. Thereby, it is possible to more effectively ensure that the total amount of charge for nerve stimulation is in a safe charge Within the amount.
  • the amplitude of the compensation pulse current signal is lower than a preset amplitude, and the period of the compensation pulse current signal is smaller than the bidirectional pulse current signal. cycle. In this case, charge compensation can be done quickly with multiple compensations.
  • a waveform of a forward pulse current signal is opposite to a waveform of a negative pulse current signal
  • the detection circuit detects the An absolute value of a charge amount of the forward pulse current signal and an amount of charge of the negative pulse current signal
  • the determination circuit comparing the charge amount of the forward pulse current signal with the charge amount of the negative pulse current signal The absolute value is used to determine whether the total amount of charge exceeds the amount of safe charge.
  • the detection circuit detects an average value of the bidirectional pulse current signal generated by the pulse current generation circuit, and the determination circuit determines the absolute value of the average value. Whether the value is greater than a preset value, and when the absolute value of the average value is greater than the preset value, the compensation circuit generates a compensation pulse current signal having a net charge amount such that the total amount of charge is within the safe charge amount . In this case, whether or not the charge compensation needs to be provided can be easily determined by detecting whether the average value is larger than a preset value.
  • the detection circuit detects a current average value of the bidirectional pulse current signal generated by the pulse current generation circuit, and converts the current average value into a voltage.
  • An average value, and the determining circuit determines whether an absolute value of the voltage average value is greater than a preset voltage value, and the compensation circuit generates a net charge when an absolute value of the voltage average value is greater than the preset voltage value.
  • the amount of compensation pulse current signal is such that the total amount of charge is within the safe charge amount.
  • the current average value can be converted into a voltage average value to be detected, and by comparing the absolute value of the voltage average value with the preset voltage value, when the absolute value of the voltage average value is greater than the preset At the voltage value, the total amount of charge that can be used for the nerve stimulation by the compensation of the compensation circuit is within the safe charge amount.
  • the compensation circuit when the absolute value of the voltage average value is greater than a preset voltage value, and the voltage average value is a positive value, the compensation circuit generates a negative The value of the net charge amount of the compensated pulse current signal for use in the nerve The total amount of the stimulus is within the safe charge amount, and when the absolute value of the voltage average value is greater than a preset voltage value, and the voltage average value is a negative value, the compensation circuit generates a positive value The compensated pulse current signal of the net charge amount is such that the total amount of charge used for nerve stimulation is within the safe charge amount.
  • the predetermined amplitude is a minimum current amplitude capable of stimulating nerve tissue. Therefore, it is possible to prevent the erroneous stimulation that the compensated pulse current signal may cause to the nerve tissue.
  • a third aspect of the present invention provides a charge compensation method which is a charge compensation method for performing charge compensation on a pulse current generation circuit, the pulse current generation circuit generating a bidirectional pulse current for nerve stimulation,
  • the charge compensation method includes: detecting a total amount of charges in one stimulation period of the bidirectional pulse current signal generated by the pulse current generation circuit; and determining that the total amount of the charges detected by the detection circuit is less than or equal to a safety charge amount And when the determination circuit determines that the total amount of charge exceeds the amount of safe charge, generating a compensated pulse current signal having a net charge amount such that the total amount of charge is within the safe charge amount.
  • a compensation pulse current signal having a negative compensation amount of charge is generated to cause the total amount of the charge to be The safe charge amount is within, and when it is judged that the total charge amount is a negative value, a compensated pulse current signal having a positive value of the compensated charge amount is generated such that the total amount of the charge is within the safe charge amount.
  • a fourth aspect of the invention provides an implantable retinal electrical stimulator, comprising: an implant device having at least the pulse current generating circuit or the charge compensation circuit according to any one of the above; and an image pickup device for Capturing a video image and converting the video image into a visual signal; a video processing device coupled to the camera device and processing the visual signal to generate a modulated signal; and an analog signal transmitting device that Transmitting a signal to the implant device, the implant device converting the received modulated signal into the bi-directional pulse current signal as an electrical stimulation signal, thereby releasing a ganglion cell or a bipolar cell of the retina
  • the bidirectional pulse current signal is used to generate a light sensation.
  • the present invention it is possible to generate a more effective stimulation effect, and it is possible to adapt to higher processing requirements such as stimulation algorithm optimization at the hardware level, and the charge compensation circuit is active. Compensating for the excess net charge that may be present on nerve tissue (such as ganglion cells or bipolar cells) can increase the efficiency of charge balance on stimulating charges and ensure the safety and reliability of nerve stimulation. In addition, it is possible to sufficiently improve the charge balance capability in a limited space without using a large capacitance occupying a large area.
  • FIG. 1 is a schematic structural view showing an implantable retinal electrical stimulator according to a first embodiment of the present invention
  • FIG. 2 is a schematic view showing the implantation of a stimulation electrode structure of an implantable retinal electrical stimulator according to the first embodiment of the present invention into an eyeball;
  • FIG 3 is a partial schematic view showing the stimulation electrode structure (stimulation end) shown in Figure 2 attached to the retina in the eyeball;
  • FIG. 4 is a schematic diagram showing a circuit block of a pulse current generating circuit for nerve stimulation according to the first embodiment of the present invention
  • FIG. 5 is a schematic diagram showing a bidirectional pulse current signal according to the first embodiment of the present invention.
  • FIG. 6 is a schematic diagram showing a circuit block of a current generator according to a first embodiment of the present invention.
  • FIG. 7 is a schematic view showing the accuracy of different pulse current amplitudes according to the first embodiment of the present invention.
  • 8a to 8d are schematic diagrams showing stimulation waveforms of different bidirectional pulse currents
  • FIG. 9 is a block diagram showing a configuration of a pulse current generation circuit according to a second embodiment of the present invention.
  • FIG. 10 is a schematic block diagram showing a charge compensation circuit according to a second embodiment of the present invention.
  • FIG. 11 is a schematic view showing a compensation pulse current according to a second embodiment of the present invention.
  • FIG. 12 is a circuit configuration diagram showing a charge compensation circuit according to a second embodiment of the present invention.
  • FIG. 1 is a schematic structural view showing an implantable retinal electrical stimulator according to a first embodiment of the present invention.
  • FIG. 2 is a schematic view showing the implantation of the stimulation electrode structure of the implantable retinal electrical stimulator according to the first embodiment of the present invention into the eyeball.
  • Fig. 3 is a partial schematic view showing the stimulation electrode structure (stimulation end) shown in Fig. 2 attached to the retina in the eyeball.
  • an implantable retinal electrical stimulator (also sometimes referred to as “artificial retina”, “artificial retinal system”) 1 may include an implanted portion, ie, an implant device 10, and an extracorporeal portion. This is the extracorporeal device 30.
  • the implant device 10 and the extracorporeal device 30 can be coupled wirelessly.
  • implant device 10 and extracorporeal device 30 can be coupled to transmit antenna 33 via receive antenna 13 shown in FIG.
  • the coupling manner of the implant device 10 and the extracorporeal device 30 is not limited thereto.
  • the implant device 10 and the extracorporeal device 30 may also be implemented by infrared receiving.
  • the implant device 10 primarily includes a substrate (not shown) and an electronic package 11, a stimulation electrode structure 12, and a receiving antenna 13 disposed on the substrate. Additionally, the base in the implant device 10 can be secured to the eyeball 20 by, for example, stitching.
  • the stimulation end 12a (stimulation electrode array) of the stimulation electrode structure 12 in the implant device 10 can enter the vitreous cavity of the eyeball 20 via the incision of the eyeball 20 and be in close proximity to the retina so as to be able to (especially ganglion cells or bipolar cells of the retina) are electrically stimulated (eg, bidirectional pulsed current is delivered) (see Figure 3).
  • the stimulation end 12a of the stimulation electrode structure 12 corresponds to the action of replacing the photoreceptor cells, and the stimulation end 12a is generated by generating an electrical stimulation signal.
  • a bidirectional pulse current signal is issued to stimulate retinal ganglion cells or bipolar cells (see Figure 3).
  • ganglion cells or bipolar cells are stimulated by electrical stimulation signals generated by stimulation electrode structure 12. Thereafter, the electrical stimulation signal is transmitted to the cerebral cortex via the well-preserved downstream visual pathway (optical nerve) and produces a light sensation, thereby partially restoring the patient's vision.
  • RP retinitis pigmentosa
  • AMD age-related macular degeneration
  • the present embodiment focuses on the optic nerve stimulation of the implantable retinal electrical stimulator, the present embodiment is not limited to the field of artificial retina, and conversely, the pulse current generating circuit according to the present embodiment 100 can also be applied to other areas of nerve stimulation such as cochlear implants, deep brain stimulation, cardiac pacemakers, spinal cord stimulators, and the like.
  • the extracorporeal device 30 may include an imaging device 31, a video processing device 32, and a transmitting antenna 33.
  • the camera device 31 can be used to capture a video image and convert the captured video image into a visual signal.
  • the camera device 31 may be a device having an imaging function such as a video camera, a digital camera, a CCD camera, or the like.
  • an imaging function such as a video camera, a digital camera, a CCD camera, or the like.
  • the imaging device 31 for example, an image of the outside world can be captured.
  • a smaller camera can be embedded in the glasses.
  • the camera device 31 can also use Google glasses. Wait to achieve.
  • an image may be acquired by using ultrasonic imaging (for example, sonar) or electromagnetic wave imaging (for example, radar), or other devices capable of generating range and angle information may be used.
  • the video processing device 32 is connected to the camera device 31 and receives the visual signal provided by the camera device 31. After the visual signal captured by the camera device 31 is passed to the video processing device 32, the video processing device 32 can process the visual signal.
  • video processing device 32 may include a microprocessor, an application specific integrated circuit (ASIC), DSP, etc. to image process (eg, sample, encode, modulate, filter, etc.) the visual signal.
  • ASIC application specific integrated circuit
  • DSP digital signal processing circuit
  • video processing device 32 also has a power supply that can provide an energy signal to implant device 10, such as via wireless transmission, to provide power to implant device 10 implanted within eyeball 20.
  • the analog signal transmitting device i.e., transmitting antenna 33
  • the analog signal transmitting device can transmit the energy signal provided by video processing device 32 and the processed visual signal as a modulated signal (e.g., an RF modulated signal) to implant device 10 of the artificial retina.
  • a modulated signal e.g., an RF modulated signal
  • the implant device 10 can be configured to receive a modulated signal transmitted by the video processing device 32 via, for example, a transmit antenna 33, and further process the modulated signal to generate a bi-directional pulse current as a stimulus current for nerve stimulation (stimulation) signal).
  • the receiving antenna 13 shown in FIG. 1 receives the modulated signal and transmits it to the subsequent electronic package 11 for processing.
  • an electrical stimulation signal will be generated by the electronic package 11 (specifically the processing circuitry within the electronic package 11) according to the modulation signal and transmitted to the stimulation end 12a (eg, the stimulation electrode array) of the stimulation electrode structure 12, thereby enabling
  • the ganglion cells or bipolar cells are stimulated (see Figure 3), and the ganglion cells or bipolar cells generate an excitation response after receiving a pulsed current to produce a light sensation.
  • the stimulation current may stimulate the ganglion cells of the retina or the bipolar cells of the retina, and may also stimulate the ganglion cells or bipolar cells of the retina at the same time.
  • FIG. 4 is a schematic diagram showing a circuit block of a pulse current generating circuit for nerve stimulation according to the first embodiment of the present invention.
  • FIG. 5 is a schematic diagram showing a bidirectional pulse current signal according to the first embodiment of the present invention.
  • the pulse current generating circuit 100 for nerve stimulation may include an analog signal receiving device 101, an analog to digital converter 102, a current signal controller 103, and a current generator 104.
  • the pulse current generating circuit 100 can be applied to the implantable retinal electrical stimulator shown in FIG. 1.
  • the pulse current generating circuit 100 can be located within the implant device 10 shown in FIG.
  • pulsed current generating circuit 100 can generate a bi-directional pulsed current signal for stimulating retinal ganglion cells or bipolar cells. Further, in some examples, the bidirectional pulse current signal generated by the pulse current generating circuit 100 can be distributed to a ganglion such as a retina by the stimulation end 12a (refer to FIG. 2) of the stimulation electrode structure 12 disposed in the implant device 10. Cells or bipolar cells.
  • the analog signal receiving apparatus 101 is configured to receive an analog signal, and may take the form of an antenna.
  • the analog signal receiving device 101 transmits the received analog signal to the analog to digital converter 102.
  • the analog signal receiving device 101 may be the receiving antenna 13 composed of a receiving coil.
  • the coil of the receiving antenna 13 may be wound by a metal wire such as gold.
  • the number of turns of the coil of the receiving antenna 13 is not particularly limited and can be set as needed.
  • the analog to digital converter 102 can convert the analog signal received by the analog signal receiving device 101 into a digital control signal and transmit the digital control signal to the current signal controller 103.
  • the circuit configuration of the analog-digital converter 102 is not particularly limited, and an A/D converter of different resolutions such as 4 bits, 6 bits, 8 bits, 10 bits, 14 bits, and 16 bits may be used as needed.
  • the analog-to-digital converter 102 may employ a successive approximation type A/D converter, a parallel comparison type A/D converter, or an integral type A/D converter.
  • the digital control signal can be a stream of digital signals indicative of pulse current parameters of the subsequently generated bi-directional pulsed current signal.
  • the current signal controller 103 can generate a pulse current parameter for generating a bidirectional pulse current signal based on the digital control signal output by the analog to digital converter 102.
  • the bidirectional pulse current as the stimulation signal may include a forward pulse current and a reverse pulse current.
  • the charge of the forward pulse current of the bidirectional pulse current and the charge of the reverse pulse current generally need to be equal to ensure safety in the stimulation of nerve tissue. The effect of bidirectional pulse current on nerve stimulation is described in more detail later.
  • the bidirectional pulse current can be a square wave type bidirectional pulse current.
  • the pulse current parameter of the bidirectional pulse current may include a negative pulse width t1, a negative pulse amplitude I1, a forward pulse width t2, a forward pulse amplitude I2, and a pulse interval t3 (see FIG. 5).
  • the pulse interval t3 refers to the time interval between the negative pulse and the forward pulse.
  • the time T is a stimulation period T described later.
  • the current signal controller 103 can generate a pulse current parameter for generating a bidirectional pulse current signal based on the digital control signal.
  • the digital control signal can instruct the current controller 103 to generate a bidirectional pulse current having a negative negative pulse width t1 that is wider (eg, t1 > t2).
  • the digital control signal can indicate current control
  • the device 103 generates a bidirectional pulse current having a small negative pulse amplitude I1 (for example, I1 ⁇ I2).
  • the current generator 104 can generate a bidirectional pulse current signal for nerve stimulation based on the pulse current parameter.
  • the pulse current generation circuit 100 for nerve stimulation can maintain the high precision of the pulse current while increasing the width of the stimulation pulse current, it is possible to provide a more effective current stimulation effect, for example, to effectively stimulate Bipolar cells to the retina.
  • a wider pulse modulation range can be realized, it is possible to adapt to higher processing requirements such as stimulation algorithm optimization and the like at the hardware level.
  • the current generator 104 can generate at least two different precision pulse currents according to the pulse current parameters. In some examples, current generator 104 is capable of generating two different precision pulsed currents. In other examples, current generator 104 is capable of generating three, four, five, or more different precision pulsed currents. In addition, the different precision multiples between adjacent different pulse currents may be twice, for example, the current generator 104 generates the first pulse current, the second pulse current, the third pulse current, the fourth pulse current, and the fifth pulse current. In the case of five different precision pulse currents, the accuracy of the fifth pulse current is twice the accuracy of the fourth pulse current, and the accuracy of the fourth pulse current is twice the accuracy of the third pulse current, and the accuracy of the third pulse current. It is twice the accuracy of the second pulse current, and the accuracy of the second pulse current is twice the accuracy of the first pulse current. Further, the present embodiment is not limited to this, and other pulse currents of different precisions may be employed.
  • the current generator 104 when the current generator 104 performs nerve stimulation on a nerve tissue or the like, it corresponds to the impedance load 110 being connected.
  • the pulse current generation circuit 100 according to the present embodiment is used for nerve stimulation of an artificial retina
  • ganglion cells or bipolar cells of the retina in the human tissue fluid can be simplified equivalently to the impedance load 110.
  • FIG. 6 is a schematic diagram showing a circuit block of the current generator according to the first embodiment of the present invention.
  • FIG. 7 is a schematic diagram showing the accuracy of different pulse current amplitudes according to the first embodiment of the present invention.
  • 8a to 8d are schematic diagrams showing stimulation waveforms of different bidirectional pulse currents
  • current generator 104 can include N current sources.
  • the N current sources may be comprised of one reference current source 1041 and (N-1) mirror current sources (current source arrays), such as switches S1, S2, ..., respectively.
  • Switch S (N) control.
  • the switch S1, the switch S2, ..., the switch S(N) controls the magnitude of the total pulse current generated by the current generator 104, that is, the pulse amplitude of the total pulse current (forward or negative pulse amplitude). It is proportional to the number of closed switches S(N).
  • the switch S1 controls the reference current source 1041.
  • the magnitude of the pulse current can be determined by the opening and closing of (N+1) current sources, and the accuracy of the pulse current can be determined by the size of the reference current source 1041.
  • the magnitude of the reference current source 1041 is the magnitude of the pulse current accuracy. For example, if the size of the reference current source 1041 is 1 ⁇ A (microamperes), the pulse current accuracy is 1 ⁇ A, and (N-1) mirror current sources are the current source 1042, the current source 1043, ... the current source 104 (N).
  • the current values of the respective mirror current sources are the same as the current values of the reference current source 1041.
  • the current values of the respective mirror current sources in the current source 1042, the current source 1043, ..., the current source 104 (N) are equal to the reference current source 1041.
  • the current generator 104 can generate an accuracy of 1 ⁇ A pulse current with 512 kinds of pulse amplitude, that is, by controlling switch S1, switch S2, ..., switch S(N), current generator 104 can generate 512 kinds of 1 ⁇ A, 2 ⁇ A, 3 ⁇ A, ..., 512 ⁇ A Different current amplitudes.
  • the current generator 104 can generate accuracy.
  • current generator 104 can generate 4 ⁇ A, 8 ⁇ A, 12 ⁇ A, ... 512 ⁇ A total 128 Different current amplitudes.
  • the current generator 104 can generate accuracy.
  • the current generator 104 can generate 64 kinds of 8 ⁇ A, 16 ⁇ A, 24 ⁇ A, ... 512 ⁇ A.
  • the current accuracy is 1 ⁇ A, 4 ⁇ A, and 8 ⁇ A as an example.
  • the present embodiment is not limited thereto, and the pulse current generation circuit 100 according to the present embodiment may generate other precisions such as 2 ⁇ A, 6 ⁇ A, and 12 ⁇ A. Current.
  • the accuracy of the generated pulse current can be set by setting a plurality of different reference current sources. Therefore, it is possible to generate a plurality of pulse currents of different precisions.
  • two different reference current sources can be provided, in which case two different precision (high precision and low precision) pulse currents can be realized.
  • the current generator 104 can generate two different precision bidirectional pulse currents, a first pulse amplitude accuracy (high precision) and a second pulse amplitude accuracy (low precision).
  • the first pulse amplitude accuracy can be 1 ⁇ A/step
  • the current amplitude range is 0-8 ⁇ A
  • the second pulse amplitude accuracy is 8 ⁇ A/step
  • the accuracy of the pulse amplitude of the high-precision pulse current (the first pulse amplitude accuracy is 1 ⁇ A/step) is greater than the accuracy of the pulse amplitude of the low-precision pulse current (the second pulse amplitude accuracy is 8 ⁇ A/step).
  • the current generator 104 can generate pulse currents of different precision according to actual conditions to meet the requirements of different nerve stimulation signals. Additionally, in other examples, current generator 104 is capable of providing more pulsed currents of different precisions.
  • the total amount of charge within one stimulation period T of the bi-directional pulsed current signal generated by current generator 104 is within a safe charge amount (eg, the total amount of charge is zero).
  • a safe charge amount eg, the total amount of charge is zero.
  • the total amount of charge in T is within the amount of safe charge.
  • the "safe charge amount” is the maximum value that a nerve tissue (such as a ganglion cell or a bipolar cell of the retina) can withstand a net charge within a safe range. A net charge that exceeds this safe charge amount may cause damage to nerve tissue.
  • one stimulation period T is a cycle time at which a stimulation signal is generated. Therefore, in the actual nerve stimulation process, it is necessary to ensure that the total amount of charge in one stimulation period T is controlled within the safe charge amount.
  • one stimulation period T is a cycle time at which a stimulation signal is generated. Total charge means The total amount of charge of the net charge in a stimulation period T of the bidirectional pulse current signal. In some examples, the amount of safe charge may also be zero for convenience.
  • FIGS. 8a to 8d show schematic diagrams of stimulation waveforms for different bidirectional pulsed currents. Since the negative pulse current is generally used as an effective stimulation signal in the field of nerve stimulation, a variation of the bidirectional pulse current signal is exemplified by a negative pulse waveform in FIGS. 8a to 8d.
  • the bidirectional pulse current signal as the stimulation waveform, although the waveform of the negative pulse and the waveform of the forward pulse are not necessarily the same, as long as the bidirectional pulse current signal is guaranteed within one stimulation period T
  • the total amount of charge can be within the amount of safe charge.
  • the negative pulse widths t11, t12, t13, and t14 may each be greater than the forward pulse width t2, thereby enabling a wide stimulation pulse.
  • the bidirectional pulse current may be a bidirectional square wave pulse current signal, a cosine pulse current signal, or a combination of a square wave and a cosine pulse current signal.
  • the current generator 104 can generate a bidirectional pulse current signal based on the pulse current parameter.
  • the bi-directional pulse current signal can include an active stimulation current signal and a balanced current signal.
  • the effective stimulation current signal is a current signal stimulating to a nerve stimulation target such as a ganglion cell or a bipolar cell;
  • the balance current signal is a current signal for balancing the charge generated by the effective stimulation current signal.
  • the effective stimulation signal is a positive pulse
  • the balanced current signal is a negative pulse; if the effective stimulation signal is a negative pulse, the balanced current signal is a positive pulse.
  • the current signal controller 103 generates a pulse current parameter for generating a bidirectional pulse current signal.
  • the pulse current parameter by setting the pulse current parameter, the total amount of charge of the bidirectional pulse current signal theoretically generated by the current generator 104 in one stimulation period is within the safe charge amount.
  • the bidirectional pulse current signal is usually set such that only one of the forward pulse and the negative pulse is the stimulation signal, and the other is the balanced current signal, thereby ensuring The total amount of charge of the bidirectional pulse current signal during one stimulation period T is within the safe charge amount.
  • the integration of the negative pulse signal of the bidirectional pulse current signal in time may be equal to the absolute value of the integration of the forward pulse signal of the bidirectional pulse current signal in time, thereby The total amount of charge of the bidirectional pulse current signal in one stimulation period T is within the safe charge amount.
  • the duration of the negative pulse signal (negative pulse width) is t1
  • the duration of the forward pulse signal (forward pulse width) is T2
  • the absolute value of the integral of the negative pulse in the duration of t1 is equal to the absolute value of the integral of the forward pulse in the duration of t2, that is, the total amount of charge of the bidirectional pulse current signal is within the amount of safe charge (for example, the total amount of charge) Zero).
  • the current generator 104 provides two different pulse amplitude precisions, a first pulse amplitude accuracy and a second pulse amplitude accuracy, wherein the first pulse amplitude accuracy is 1 ⁇ A/step and the amplitude range is 0 to 8 ⁇ A (for example, 1 ⁇ A, 2 ⁇ A, 3 ⁇ A, ..., 8 ⁇ A); the second pulse amplitude accuracy is 8 ⁇ A/step, and the amplitude ranges from 8 to 512 ⁇ A (for example, 8 ⁇ A, 16 ⁇ A, 24 ⁇ A, ..., 512 ⁇ A) (see Fig. 7).
  • the first pulse amplitude accuracy is 1 ⁇ A/step and the amplitude range is 0 to 8 ⁇ A (for example, 1 ⁇ A, 2 ⁇ A, 3 ⁇ A, ..., 8 ⁇ A)
  • the second pulse amplitude accuracy is 8 ⁇ A/step
  • the amplitude ranges from 8 to 512 ⁇ A for example, 8 ⁇ A, 16
  • the current generator 104 can provide a higher precision pulse amplitude accuracy (eg, 1 [mu]A /step), for example, when the current amplitude required by ganglion cells or bipolar cells is less than or equal to 8 ⁇ A, a pulse amplitude accuracy of 1 ⁇ A/step is generated, which can provide 1 ⁇ A, 2 ⁇ A, 3 ⁇ A, 4 ⁇ A, 5 ⁇ A, 6 ⁇ A, 7 ⁇ A, 8 ⁇ A total of 8 pulse amplitude currents; when the current required by ganglion cells or bipolar cells is greater than 8 ⁇ A, a pulse amplitude accuracy of 8 ⁇ A/step current is generated, which can provide 16 ⁇ A, 24 ⁇ A, 32 ⁇ A, 40 ⁇ A, ... 512 ⁇ A 64 pulse amplitude currents.
  • a pulse amplitude accuracy eg, 1 [mu]A /step
  • the current generator 104 is capable of providing pulse amplitudes of at least two different precisions, generating at least two different precision pulse currents, thereby enabling a more efficient current stimulation mode.
  • current generator 104 can generate a low precision pulse current or a high precision pulse current based on the pulse current parameter. Specifically, after receiving the pulse current parameter, the current generator 104 determines whether the pulse amplitude of the bidirectional pulse current signal to be generated is less than a critical value. When the pulse amplitude of the bidirectional pulse current signal to be generated is less than or equal to a critical value, the current generator 104 generates a high precision pulse current; when the pulse amplitude of the bidirectional pulse current signal to be generated is greater than a critical value, the current generator 104 generates a low Precision Pulse current. Thereby, the current generator 104 can generate corresponding pulse currents under different conditions to meet the requirements of different nerve stimulation signals.
  • the threshold value can be set in advance.
  • the amplitude accuracy of the high-precision pulse current and the amplitude accuracy of the low-precision pulse current can also be set in advance.
  • the threshold value can be set to 8 ⁇ A
  • the amplitude accuracy of the high-precision pulse current is 1 ⁇ A/step
  • the amplitude accuracy of the low-precision pulse current is 8 ⁇ A/step.
  • the current generator 104 determines that the amplitude of the bidirectional pulse current signal to be generated is less than or equal to 8 ⁇ A, the current generator 104 generates a high-precision (1 ⁇ A/step) pulse current; when the current generator 104 determines that it is to be generated When the amplitude of the bidirectional pulse current signal is greater than 8 ⁇ A, the current generator 104 generates a low precision (8 ⁇ A/step) pulse current. In this way, the current generator 104 can provide two different precision pulse currents, and when the pulse current required by the ganglion cells or the bipolar cells is small, providing a high-precision pulse current can more accurately stimulate the bipolar cells of the retina. Can provide a more efficient way to stimulate.
  • the current generator 104 when the forward pulse width of the bidirectional pulse current signal is greater than a preset duration and the forward pulse amplitude is less than a critical value, or when the negative pulse width of the bidirectional pulse current signal is greater than a preset duration and the negative pulse amplitude is less than At the critical value, the current generator 104 produces a high precision pulse current.
  • the width of the stimulation pulse current (stimulation time)
  • the mechanism of action is still not fully understood, by prolonging the stimulation pulse width (for example, the negative pulse width), it is more likely to stimulate deeper nerve cells, thereby enabling more Effective nerve stimulation.
  • a wide stimulation pulse can stimulate bipolar cells to the retina more efficiently, thereby providing more effective and precise nerve stimulation.
  • the bidirectional pulse current signal when the negative pulse width of the bidirectional pulse current signal is greater than a preset duration and the negative pulse amplitude is less than a critical value, the bidirectional pulse current signal can more accurately stimulate the bipolar cells of the retina due to bipolar cells in One-to-one correspondence in visual pathways is superior to ganglion cells, so accurate stimulation of bipolar cells can result in a more accurate light perception.
  • the current generator 104 produces high precision The pulse current, precise stimulation of bipolar cells, creates a more accurate light perception, which can provide a more efficient stimulation for the blind.
  • FIG. 9 is a circuit configuration diagram showing a pulse current generation circuit according to a second embodiment of the present invention.
  • FIG. 10 is a circuit configuration diagram showing a charge compensation circuit according to a second embodiment of the present invention.
  • FIG. 11 is a schematic view showing a compensation pulse current according to a second embodiment of the present invention.
  • FIG. 12 is a circuit configuration diagram showing a charge compensation circuit according to a second embodiment of the present invention.
  • the pulse current generation circuit 200 differs from the pulse current generation current 100 according to the first embodiment in that it includes the analog signal receiving device 101, the analog-to-digital converter 102, and the current signal according to the first embodiment.
  • a charge compensation circuit 106 is also included.
  • the present embodiment focuses on the optic nerve stimulation of the implantable retinal electrical stimulator, the present embodiment is not limited to the field of artificial retina, and conversely, the charge compensation circuit 106 according to the present embodiment. It can also be applied to other areas of nerve stimulation such as cochlear implants, deep brain stimulation, cardiac pacemakers, spinal cord stimulators, and the like.
  • the charge compensation circuit 106 for nerve stimulation can be applied to the implantable retinal electrical stimulator shown in FIG.
  • the charge compensation circuit 106 can be located within the implant device 10 shown in FIG. 1 (eg, within the electronic package 11).
  • the pulse current generating circuit 200 may be located in the electronic package 11 shown in FIG.
  • the charge compensation circuit 106 can be used to charge compensate the pulse current generation circuit 200.
  • a charge compensation circuit (also referred to as "active charge compensation circuit") 106 includes a detection circuit 1061, a determination circuit 1062, and a compensation circuit 1063.
  • the detection circuit 1061 can be used to detect the total amount of charge in one stimulation period T of the bidirectional pulse current signal generated by the pulse current generation circuit 200.
  • the determination circuit 1062 can be used to determine whether the total amount of charge detected by the detection circuit 1061 exceeds a safe charge amount.
  • the compensation circuit 1063 can be used to generate a compensated pulse current signal having a net charge amount when the judgment circuit 1062 determines that the total amount of charge exceeds the safe charge amount so that the total amount of charge used for the nerve stimulation is within the safe charge amount.
  • the amount of net charge may be a negatively charged amount of charge or a positively charged amount depending on the amount of compensation required.
  • the bidirectional pulse can be made by setting the pulse current parameter of the bidirectional pulse current signal (for example, the pulse current parameter can include a forward pulse width, a forward pulse amplitude, a negative pulse width, a negative pulse amplitude, a pulse interval, etc.)
  • the pulse current parameter can include a forward pulse width, a forward pulse amplitude, a negative pulse width, a negative pulse amplitude, a pulse interval, etc.
  • the total amount of charge of the current signal during one stimulation period T is within the safe charge amount.
  • the bidirectional pulse current signal generated by the pulse current generating circuit 200 is likely to exceed the safe charge amount due to various factors in a total stimulation period T. In this case, the net charge accumulated by the bidirectional pulse current signal may cause damage to human ocular ganglion cells or bipolar cells.
  • the charge compensation circuit 106 actively compensates for the excess net charge accumulated on the nerve tissue (for example, ganglion cells or bipolar cells), thereby improving the charge balance ability to the stimulus charge and ensuring the safety of the nerve stimulation. And reliability. This serves to protect human neural tissue such as retinal ganglion cells or bipolar cells.
  • the detection circuit 1061 can be used to detect the total amount of charge in one stimulation period T of the bidirectional pulse current signal generated by the pulse current generation circuit 200.
  • the judging circuit 1062 judges whether or not the total amount of electric charge in one stimulation period T of the bidirectional pulse current signal detected by the detecting circuit 1061 exceeds the safe electric charge amount. If the total amount of charge in one stimulation period T of the bidirectional pulse current signal is within the safe charge amount, the compensation circuit 1063 does not operate; if the total amount of charge in one stimulation period T of the bidirectional pulse current signal exceeds the safe charge amount, the compensation Circuitry 1063 generates a compensated pulsed current signal having a net amount of charge such that the total amount of charge for nerve stimulation is within the safe amount of charge.
  • the compensating circuit 1063 when the judging circuit 1062 judges that the total amount of electric charge of the bidirectional pulse current signal in one stimulation period T is a positive electric charge, the compensating circuit 1063 generates a negative current current pulse to use the total amount of electric charge for the nerve stimulation at the safety The amount of charge is within; when the judging circuit 1062 judges that the total amount of electric charge of the bidirectional pulse current signal in one stimulation period T is a negative electric charge, the compensating circuit 1063 generates a forward current pulse to use the total amount of electric charge for the nerve stimulation in the safety Within the amount of charge.
  • the compensation circuit 1063 can actively perform charge compensation. Once the judging circuit 1062 judges that the total amount of electric charge in one stimulation period generated by the pulse current generating circuit 200 detected by the detecting circuit 1061 exceeds the safe electric charge amount, the compensating circuit 1063 Charge compensation can be performed in time to improve charge balance efficiency or ability to ensure the safety of stimulated nerve tissue.
  • the compensation circuit 1063 can generate a compensated pulse current signal having a net charge amount for use in nerve stimulation. The total amount of charge is within the safe charge amount.
  • the compensation circuit 1063 can generate a compensated pulse current signal having a positive net charge amount so that the total charge for the nerve stimulation is made. The amount is within the safe charge amount.
  • the compensating circuit 1063 when the judging circuit 1062 judges that the total amount of charges in one stimulation period T of the bidirectional pulse current signal is a negative charge of -1 ⁇ 10 -7 coulomb, the compensating circuit 1063 generates a positive total amount of charges of 1 ⁇ 10 -7 coulombs.
  • the charge for example, the compensation circuit 1063 can generate a forward pulse having a pulse width of 1 millisecond and a pulse amplitude of 100 microamperes, or the compensation circuit 1063 can generate a pulse width of 10 milliseconds and a pulse amplitude of 10 microamperes.
  • the total amount of charge for nerve stimulation is within the safe charge.
  • the compensating circuit 1063 when the judging circuit 1062 judges that the total amount of electric charge in one stimulation period T of the bidirectional pulse current signal is a positive electric charge of 1 ⁇ 10 -7 coulomb, the compensating circuit 1063 generates a total electric charge of -1 ⁇ 10 -7 coulomb Negative charge (for example, compensation circuit 1063 can generate a negative pulse with a pulse width of 1 millisecond and a pulse amplitude of 100 microamperes, or compensation circuit 1063 can produce a pulse width of 10 milliseconds with a pulse amplitude of 10 microamps. The negative pulse) causes the total amount of charge for nerve stimulation to be within the safe charge amount.
  • the amplitude of the compensated pulse current signal may be lower than a preset amplitude, and the period of the compensated pulse current signal may be less than the period of the bidirectional pulse current signal.
  • the preset amplitude is a minimum current amplitude capable of stimulating nerve tissue (for example, ganglion cells or bipolar cells), by setting the amplitude of the compensation pulse current signal to be lower than a preset amplitude, This can prevent the pulse current signal from compensating for possible false stimulation of nerve tissue (such as ganglion cells or bipolar cells), and inhibiting nervous tissue (such as ganglion cells or bipolar cells) may receive compensation pulse current signals and generate unnecessary Excitement.
  • the period in which the pulse current signal is compensated is compensated for less than the period of the bidirectional pulse current signal.
  • the charge compensation can be performed in a shorter time, and the charge compensation can be quickly performed, for example, by multiple compensation.
  • the waveform of the forward pulse current signal in the bidirectional pulse current signal may be opposite to the waveform of the negative pulse current signal. That is, in the bidirectional pulse current signal, the waveform of the forward pulse current signal has the same waveform shape except that it is inverted from the negative pulse current signal.
  • the detecting circuit 1061 can detect the absolute value of the amount of charge of the forward pulse current signal and the amount of charge of the negative pulse current signal. Then, the judging circuit 1062 judges whether or not the total amount of electric charges exceeds the safe electric charge amount by comparing the electric charge amount of the forward pulse current signal with the absolute value of the electric charge amount of the negative pulse current signal.
  • FIG. 5 is a schematic diagram showing a bidirectional pulse current signal according to an embodiment of the present invention.
  • the bidirectional pulse current signal may include a forward pulse signal and a negative direction pulse signal, and the waveform of the forward pulse current signal is opposite to the waveform of the negative pulse current signal.
  • the detecting circuit 1061 can detect the absolute value of the amount of charge of the forward pulse current signal and the amount of charge of the negative pulse current signal.
  • is the absolute value of I2 ⁇ t2.
  • the amount of charge Q1 is equal to the amount of charge Q2, it is determined that the total amount of charges is zero.
  • the amount of charge Q1 and the amount of charge Q2 are not equal, it is determined that the total amount of charge is not zero, wherein when the amount of charge Q1 is greater than the amount of charge Q2, it is determined that the total amount of charge is positive (there is a net positive charge), when the amount of charge When Q1 is smaller than the charge amount Q2, it is determined that the total amount of charge is a negative value (there is a net negative charge).
  • it is only necessary to ensure that the total amount of charges described above is either a net positive charge or a net negative charge within a safe charge amount.
  • the detection circuit 1061 can detect an average of the bidirectional pulse current signals generated by the pulse current generation circuit 200. Specifically, by directly calculating the net charge amount between the negative charge amount and the positive charge amount of the bidirectional pulse current signal, and averaging the net charge amount, the bidirectional generated by the pulse current generating circuit 200 can be obtained. Whether the total charge of the pulse current signal has a net charge. Then, the determining circuit 1062 can determine whether the absolute value of the average value is greater than a preset value, and when the absolute value of the average value is greater than the preset value, the compensation circuit 1063 can generate a compensated pulse current signal having a net charge amount for use in the nerve stimulation. The total amount of charge is within the safe charge.
  • the average value of the bidirectional pulse current signal may be an average current value, an average charge value, or the like of the bidirectional pulse current signal.
  • the preset value may be a preset current value, a preset charge value, or the like.
  • the average of the bi-directional pulsed current signals can be the average current value of the bi-directional pulsed current signals.
  • the compensation circuit 1063 If I a is greater than I', the compensation circuit 1063 generates a compensated pulse current signal having a net charge amount such that the total amount of charge for nerve stimulation is within a safe charge amount; if I a is less than or equal to I', the compensation circuit 1063 does not jobs.
  • the average of the bi-directional pulse current signals can be the average charge value of the bi-directional pulse current signals.
  • the preset charge value be Q'(Q'>0)
  • the decision circuit 1062 can determine whether Q a is greater than Q'. If Q a is greater than Q', the compensation circuit 1063 generates a compensated pulse current signal having a net charge amount such that the total amount of charge used for the nerve stimulation is within the safe charge amount; if Q a is less than or equal to Q', the compensation circuit 1063 does not jobs.
  • the detection circuit 1061 may detect a current average of the bidirectional pulse current signal generated by the pulse current generation circuit 200 and convert the current average value into a voltage average value.
  • the judging circuit 1062 can judge whether or not the absolute value of the voltage average value is greater than a preset voltage value.
  • the compensation circuit 1063 may generate the compensated pulse current signal having the net charge amount so that the total amount of charge used for the nerve stimulation is within the safe charge amount.
  • the current average circuit can be used to convert the current average value into a voltage average value, and the preset voltage value is a safe voltage value.
  • the pulse current generating circuit 200 When the voltage average value is lower than the preset voltage value, the pulse current generating circuit 200 generates The bidirectional pulse current signal does not harm the ganglion cells or bipolar cells of the human body (the safety charge amount is not exceeded), the compensation circuit 1063 does not need to perform charge compensation; when the voltage average value is higher than the preset voltage value, the pulse current generation is indicated.
  • the bidirectional pulse current signal generated by the circuit 200 may cause damage to the ganglion cells or bipolar cells of the human body, and the compensation circuit 1063 generates a compensated pulse current signal having a net charge amount to use the total amount of charge for the nerve stimulation at a safe charge amount.
  • the average value of the detected current can be converted by the detecting circuit 1061 into a voltage average value that the determining circuit 1062 can easily judge (for example, the determining circuit 1062 can use the voltage comparator to determine), and the circuit can be conveniently judged. 1062 judgment Whether or not the compensation circuit 1063 is required for charge compensation is required, and the accuracy of the judgment result of the judgment circuit 1062 can be improved.
  • the compensation circuit 1063 may generate a compensated pulse current signal having a negative value of the net charge amount for use in the nerve The total amount of stimulating charge is within a safe charge amount; when the absolute value of the voltage average value is greater than the preset voltage value, and the voltage average value is a negative value, the compensation circuit 1063 generates a compensated pulse current signal having a positive value of the net charge amount. The total amount of charge used for nerve stimulation is within the safe charge.
  • the detecting circuit 1061 can detect the current average value of the bidirectional pulse current signal generated by the pulse current generating circuit 200, and convert the current average value into a voltage average value.
  • the determining circuit 1062 can determine whether the absolute value of the voltage average value is greater than a preset voltage value. When the absolute value of the voltage average value is greater than the preset voltage value, and the voltage average value is a positive value, the compensation circuit 1063 generates a net with a negative value.
  • the compensation pulse current signal of the charge amount is within a safe charge amount for the total amount of charge used for the nerve stimulation; when the absolute value of the voltage average value is greater than the preset voltage value, and the voltage average value is a negative value, the compensation circuit 1063 is generated The positive value of the net charge amount compensates for the pulse current signal so that the total amount of charge used for the nerve stimulation is within the safe charge amount.
  • the compensation circuit 1063 when the voltage average value is greater than 5 millivolts (ie, the absolute value of the voltage average value is greater than the preset voltage value, and the voltage average value is positive)
  • the compensation circuit 1063 generates a compensated pulse current signal having a negative net charge amount so that the total amount of charge used for the nerve stimulation is within a safe charge amount, for example, the compensation pulse current signal generated by the compensation circuit 1063 is a negative pulse.
  • the compensation circuit 1063 when the voltage average value is less than -5 mV (that is, when the absolute value of the voltage average value is greater than the preset voltage value, and the voltage average value is a negative value), the compensation circuit 1063 generates a net charge amount having a positive value.
  • the pulse current signal is compensated so that the total amount of charge used for the nerve stimulation is within a safe charge amount.
  • the compensation pulse current signal generated by the compensation circuit 1063 is a forward pulse.
  • FIG. 11 is a circuit configuration diagram showing a charge compensation circuit according to an embodiment of the present invention.
  • the charge compensation circuit 106 may include a detection circuit 1061, a determination circuit 1062, and a compensation circuit 1063.
  • the detection circuit 1061 may specifically include a first resistor R1, a second resistor R2, and a capacitor C1. Wherein, the negative electrode of the first capacitor and the first end of the first resistor R1 are connected to the common voltage VSS, and the positive electrode of the first capacitor and the first The second end of the resistor R1 is electrically connected to the second end of the second resistor R2, and the first end of the second resistor R2 is electrically connected to the pulse current generating circuit 200 and the compensation circuit 1063.
  • the determination circuit 1062 may specifically include the first voltage comparator U1 and the second voltage comparator U2.
  • the non-inverting input end of the first voltage comparator U1 and the non-inverting input end of the second voltage comparator U2 are electrically connected to the first end of the second resistor R2, and the inverting input end of the first voltage comparator U1 is connected to the preset positive Voltage VTH+, the inverting input terminal of the second voltage comparator U2 is connected to the preset negative voltage VTH-, and the power supply terminal of the first voltage comparator U1 and the power supply terminal of the second comparator U2 are connected to the power supply voltage VDD, the first The ground terminal of the voltage comparator U1 and the ground terminal of the second comparator U2 are both connected to the common voltage VSS, and the output terminal Out1 of the first voltage comparator U1 is electrically connected to the first control terminal C+ of the compensation circuit 1063, and the second voltage comparator The output terminal Out2 of U2 is electrically connected to the second control terminal C- of the
  • the power supply terminal of the pulse current generating circuit 200 is connected to the power supply voltage VDD, the ground terminal of the pulse current generating circuit 200 is connected to the common voltage VSS, and the output terminal of the pulse current generating circuit 200 is connected to the impedance load 110.
  • the detecting circuit 1061 can detect the total amount of electric charge of the bidirectional pulse current signal generated by the pulse current generating circuit 200 in one stimulation period T and the current average value in one stimulation period T, and average the current in one stimulation period T. Convert to voltage average.
  • the determining circuit 1062 can determine whether the voltage average value is between the preset positive voltage VTH+ and the preset negative voltage VTH-.
  • the compensation circuit 1063 does not need to perform charge compensation; if the above voltage average value is not between the preset positive voltage VTH+ and the preset negative voltage VTH-, the compensation circuit 1063 performs charge compensation to generate a compensated pulse current signal having a net charge amount to use The total amount of charge in the nerve stimulation is within the safe charge.
  • the detection circuit 1061 can be used to detect the total amount of charge of the bidirectional pulse current signal generated by the current generator 104 during one stimulation period T.
  • detection circuit 1061 can be comprised of an integration circuit. The integrating circuit can integrate the electric charge of the bidirectional pulse current signal generated by the current generator 104 in one stimulation period T, thereby obtaining the total amount of electric charge of the bidirectional pulse current signal in one stimulation period T.
  • the compensation circuit 1063 performs charge compensation. That is, when the current average value of the bidirectional pulse current signal is greater than 5 ⁇ 10 -7 mA or less than -5 ⁇ 10 -7 mA, the compensation circuit 1063 performs charge compensation. If the resistance of the second resistor R2 is 10 kohms, the preset positive voltage VTH+ can be 5 millivolts, and the preset negative voltage VTH- is -5 millivolts.
  • the determining circuit 1062 determines that the average value of the voltage exceeds 5 millivolts, the output terminal Out1 of the first voltage comparator U1 outputs a high level, and the output terminal Out2 of the second voltage comparator U2 outputs a high level; when the determining circuit 1062 determines When the average value of the voltage is lower than -5 mV, the output terminal Out1 of the first voltage comparator U1 outputs a low level, and the output terminal Out2 of the second voltage comparator U2 outputs a low level; when the judging circuit 1062 judges the above voltage average When the value is between -5 mV and 5 mV, the output terminal Out1 of the first voltage comparator U1 outputs a low level, and the output terminal Out2 of the second voltage comparator U2 outputs a high level.
  • the compensation pulse current signal outputted from the output terminal of the compensation circuit 1063 is related to the first control terminal C+ of the compensation circuit 1063 and the second control terminal C- of the compensation circuit 1063, see Table 1 below.
  • the first control terminal C+ The second control terminal C- Compensation pulse current signal High level High level Negative pulse Low level Low level Positive pulse Low level High level no
  • the compensation circuit 1063 needs to compensate for the negative pulse.
  • the output terminal Out1 of the first voltage comparator U1 outputs a high level, and the output of the second voltage comparator U2.
  • the terminal Out2 outputs a high level, that is, the first control terminal C+ is at a high level, and the second control terminal C- is at a high level.
  • the compensation pulse current signal generated by the compensation circuit 1063 is a negative pulse.
  • the compensation circuit 1063 needs to compensate for the forward pulse.
  • the output terminal Out1 of the first voltage comparator U1 outputs a low level, and the second voltage is compared.
  • the output terminal Out2 of the device U2 outputs a low level, that is, the first control terminal C+ is low level, and the second control terminal C- is low level.
  • the compensation pulse current signal generated by the compensation circuit 1063 is positive. To the pulse.
  • the compensation circuit 1063 does not need to perform charge compensation, and the output terminal Out1 of the first voltage comparator U1 outputs a low level, the second voltage.
  • the output terminal Out2 of the comparator U2 outputs a high level, that is, the first control terminal C+ is at a low level, and the second control terminal C- is at a high level. As shown in Table 1, the compensation circuit 1063 does not perform charge compensation.
  • FIG. 11 is only a specific charge compensation circuit according to a preferred embodiment of the present invention, and the present embodiment is not limited thereto.
  • the specific implementation of the detection circuit 1061, the determination circuit 1062, and the compensation circuit 1063 can be variously modified.
  • the charge compensation method is a charge compensation method for performing charge compensation on the pulse current generation circuit 200, and the pulse current generation circuit 200 generates a bidirectional pulse current for nerve stimulation, and the charge compensation method includes: detection by The total amount of charge in one stimulation period of the bidirectional pulse current signal generated by the pulse current generating circuit 200; determining that the total amount of charge detected by the detecting circuit 1061 is less than or equal to the amount of safe charge; and when the determining circuit 1062 determines that the total amount of charge exceeds the safe charge At the time of the quantity, a compensated pulse current signal having a net charge amount is generated to make the total amount of charge within the safe charge amount.
  • a compensation pulse current signal having a negative compensation amount of charge is generated to make the total amount of charge within a safe charge amount, and when the total charge amount is judged to be negative At the time of the value, a compensated pulse current signal having a positive value of the compensated charge is generated such that the total amount of charge is within the safe charge amount.
  • the compensation circuit 1063 when the determining circuit 1062 determines that the total amount of charge of the bidirectional pulse current signal in one stimulation period T is positive, the compensation circuit 1063 performs negative charge compensation on the bidirectional pulse current signal generated by the current generator 104; The circuit 1062 determines that the total amount of charge of the bidirectional pulse current signal during one stimulation period T is a negative charge, and the compensation circuit 1063 can generate a forward current pulse to positively compensate the bidirectional pulse current signal generated by the current generator 104.
  • the compensation circuit 1063 can preferably adopt a successive approximation charge compensation method, whereby the charge compensation can be performed step by step, and the accuracy of the charge compensation can be improved.
  • the compensation circuit 1063 can generate a small current pulse to perform multiple charge compensation on the bidirectional pulse current signal generated by the current generator 104.
  • the net charge amount of the small current pulse generated by the compensation circuit 1063 may be positive or negative.
  • the charge compensation can be performed step by step using the charge convergence compensation method to improve the accuracy of charge compensation.
  • the detection circuit 1061 can detect the total amount of charge of the bidirectional pulse current signal generated by the pulse current generation circuit 200 during one stimulation period T.
  • the judging circuit 1062 can judge whether the absolute value of the total amount of electric charge of the bidirectional pulse current signal in one stimulation period T is greater than the safe electric quantity, and the judging circuit 1062 judges the absolute value of the total electric charge amount of the bidirectional pulse current signal in one stimulation period T.
  • the compensation circuit 1063 performs partial charge compensation.
  • the compensation circuit 1063 performs partial charge compensation.
  • the partial charge compensation here can be proportional charge compensation, for example, charge compensation according to proportional values of 30%, 40%, 50%, 60%, 70%, 80%.
  • the compensation circuit 1063 can follow The positive charge compensation is performed at a ratio of 50%, that is, the compensation circuit 1063 can perform positive charge compensation of 5 ⁇ 10 -8 coulombs. Then, the detecting circuit 1061 can continue to detect the total amount of charges accumulated by the pulse current generating circuit 200.
  • the compensation circuit 1063 Positive charge compensation of 3 ⁇ 10 -8 coulomb was performed. Thereafter, the detecting circuit 1061 continues to detect the total amount of charges accumulated by the pulse current generating circuit 200, and when the determining circuit 1062 determines that the total amount of charges accumulated by the pulse current generating circuit 200 exceeds the safe charge amount (5 ⁇ 10 -8 ), the compensation circuit 1063 continues to perform charge compensation in a 50% ratio until the determination circuit 1062 determines that the absolute value of the total amount of charge accumulated by the pulse current generation circuit 200 is within the safe charge amount, the compensation circuit 1063 stops performing charge compensation.
  • the detecting circuit 1061 can continue to detect the total amount of charges accumulated by the pulse current generating circuit 200, that is, the detecting circuit 1061 can be always in the working state and perform detection in real time. Once the amount of charge is detected to be excessive (the absolute value of the total amount of charge generated by the pulse current generating circuit 200 is greater than the amount of safe charge), the compensation circuit 1063 can perform charge compensation.
  • the detection circuit 1061 can detect the total amount of charge of the bidirectional pulse current signal generated by the pulse current generation circuit 200 during one stimulation period T.
  • the judging circuit 1062 can determine whether the total amount of electric charge of the bidirectional pulse current signal in one stimulation period T is Exceeding the amount of safe charge.
  • the compensating circuit 1063 can perform partial electric charge compensation. For example, when the judging circuit 1062 determines that the total amount of electric charge of the bidirectional pulse current signal in one stimulation period T is Q1, and Q1 exceeds the safe electric charge amount, the compensation circuit 1063 can perform partial charge compensation, where the partial charge compensation can be a proportional charge. For compensation, for example, charge compensation is performed at a proportional value of 30%, 40%, 50%, 60%, 70%, 80%.
  • the positive electric charge replenishment can be performed at a ratio of 50%, that is, the compensating circuit 1063 performs 5 ⁇ 10 -8 Coulomb's negative charge compensation. Then, the detecting circuit 1061 can continue to detect the total amount of charges accumulated by the pulse current generating circuit 200. If the judging circuit 1062 judges that the total amount of charges accumulated by the pulse current generating circuit 200 is a positive charge of 6 ⁇ 10 -8 coulomb, the compensating circuit 1063 can continue the negative electric charge compensation of 3 ⁇ 10 -8 coulomb.
  • the detecting circuit 1061 can continue to detect the total amount of charges accumulated by the pulse current generating circuit 200.
  • the compensating circuit 1063 can continue to perform electric charge compensation at a ratio of 50% until the judging circuit 1062 judges that the pulse current generating circuit 200 cumulatively generates
  • the compensation circuit 1063 may stop performing charge compensation on the pulse current generating circuit 200.
  • the detection circuit 1061 can continue to detect the total amount of charge accumulated by the pulse current generation circuit 200. That is to say, the detecting circuit 1061 can always be in an active state and perform detection in real time. Once the detected amount of charge exceeds the amount of safe charge, the compensation circuit 1063 can perform charge compensation.

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Abstract

一种用于神经刺激的脉冲电流产生电路（100），包括：模拟信号接收装置（101），其用于接收模拟信号；模数转换器（102），其将模拟信号转换为数字控制信号；电流信号控制器（103），其根据数字控制信号产生用于生成双向脉冲电流信号的脉冲电流参数；以及电流发生器（104），其根据脉冲电流参数生成用于神经刺激的双向脉冲电流信号，电流发生器能够根据脉冲电流参数生成不同精度的脉冲电流。根据上述脉冲电流产生电路，能够产生更加有效的刺激效果，而且能够在硬件层面适应更高的处理要求例如刺激算法优化等。此外，还涉及一种电荷补偿电路、电荷补偿方法以及使用上述脉冲电流产生电路或电荷补偿电路的植入式视网膜电刺激器。

Description

用于神经刺激的脉冲电流产生电路、电荷补偿电路和方法及植入式视网膜电刺激器 技术领域
本发明涉及一种用于神经刺激的脉冲电流产生电路、电荷补偿电路和方法及植入式视网膜电刺激器。
背景技术
在神经刺激领域中，通过刺激电极提供电刺激能够使神经组织产生反应，从而获得期望的功能。例如在现有的人工视网膜的视力修复系统中，为了给盲人恢复视觉感受，一般需要在盲人的眼球内放入植入体，这样的植入体替代了例如因视网膜色素变性(RP)或老年黄斑变性(AMD)等而受损的感光细胞的功能，在视觉通路的其他功能得到保留的情况下，可以通过植入体中的刺激电极来对视网膜保留完好的其他神经通路产生刺激从而让盲人恢复部分视力。
在人工视网膜系统中，体外的摄像头捕捉视频图像，接着图像处理装置将视频图像转化为电信号并发送给植入体，然后，位于眼内的植入体将电信号转换为刺激信号，并通过植入体的刺激电极对视网膜的神经节细胞进行刺激，由此使盲人能够在大脑皮层上感受到光感，恢复部分视力。
发明内容
然而，在现有的人工视网膜或人工视网膜系统例如植入式视网膜电刺激器中，刺激电极所产生的刺激信号往往只能对视网膜表面的神经细胞(例如神经节细胞)进行刺激，无法有效地刺激到稍微远离视网膜表面的视网膜的双极细胞，因此，在刺激效果上往往并不理想，另外，在刺激的分辨率上还有很多方面有待改进。
另外，在现有的神经刺激装置例如人工视网膜系统中，所产生的用于神经刺激的刺激电流很可能不能保证在一个刺激周期内电荷量在 安全电荷量以内，被刺激的神经组织(例如视网膜的神经节细胞或双极细胞)因此有可能存在正电荷或负电荷等净电荷，导致神经组织例如视网膜的神经节细胞或双极细胞受到损伤。
为了保证神经组织例如视网膜的神经节细胞或双极细胞所接收的刺激电荷的平衡性，也有考虑在脉冲电流产生电路与被刺激部位之间设置RC电路，以平衡神经节细胞或双极细胞上多余的电荷。然而，RC电路的电荷平衡性能与RC电路中的电容的容量正相关，为了平衡较多的正电荷或负电荷，需要将RC电路中的电容的容量提升，由此需要更大面积的电容。然而，在神经刺激领域中，电路设计空间往往容易受限，无法集成面积占据较大的大电容，因此，利用RC电路来平衡电荷能力并不能充分得到发挥。
本发明人等经过长期的研究发现，在视网膜中神经节细胞与多个双极细胞相连接，而在视网膜的黄斑区(通常是人工视网膜的植入部位)双极细胞与单个感光细胞一一对应连接，通过刺激视网膜的双极细胞能够有效地提高刺激的分辨率，产生更加精准和有效的光感。对于例如视网膜上的植入式视网膜电刺激器修复方式而言，植入体内的刺激电极常常贴合在视网膜上，刺激电极能够接触的部分主要是视网膜的神经节细胞(特别是神经节细胞的轴突)。为了让刺激电极所产生的刺激信号能够刺激到与刺激电极稍远的双极细胞，一般要求刺激电极能够提供例如宽的刺激脉冲的脉冲电流。另外，从刺激电极的安全电荷量的角度看，若脉冲电流的刺激脉冲较宽，则其脉冲电流的幅度要相应地缩小，以确保刺激电荷在安全电荷量的范围内。
为了解决上述现有问题，本发明的目的在于提供了一种能够提高有效刺激分辨率的用于神经刺激的脉冲电流产生电路、电荷补偿电路和方法及植入式视网膜电刺激器。
为此，本发明的第一方面提供一种用于神经刺激的脉冲电流产生电路，包括：模拟信号接收装置，其用于接收模拟信号；模数转换器，其将所述模拟信号转换为数字控制信号；电流信号控制器，其根据所述数字控制信号产生用于生成双向脉冲电流信号的脉冲电流参数；以及电流发生器，其根据所述脉冲电流参数生成用于神经刺激的所述双向脉冲电流信号，所述电流发生器能够根据所述脉冲电流参数生成不 同精度的脉冲电流。
在本发明的第一方面中，电流信号控制器根据数字控制信号产生用于生成双向脉冲电流信号的脉冲电流参数，并且电流发生器根据脉冲电流参数生成不同精度的用于神经刺激的双向脉冲电流信号。通过能够生成不同精度的脉冲电流的电流发生器，可以根据刺激需要生成不同脉冲宽度和不同精度的双向脉冲电流信号，由此不仅能够满足安全电荷的要求，而且还可以有效刺激到所需要刺激的神经细胞(例如双极细胞)，从而能够产生更加有效的刺激效果。另一方面，由于脉冲电流产生电路能够实现更宽的脉冲信号，因此，能够在硬件层面适应更高的处理要求例如刺激算法优化等。
另外，在本发明所涉及的脉冲电流产生电路中，可选地，在一个刺激周期内，所述双向脉冲电流信号的电荷总量在安全电荷量以内。由此，能够避免脉冲电流信号对人体神经组织(例如视网膜的神经节细胞或双极细胞)造成伤害，确保脉冲电流产生电路的安全性和可靠性。
在本发明所涉及的脉冲电流产生电路中，可选地，所述脉冲电流参数包括负向脉冲宽度、负向脉冲幅度、正向脉冲宽度、正向脉冲幅度、以及脉冲间隔。由此，通过控制所述脉冲电流参数，从而能够实现不同的刺激脉冲电流。
另外，在本发明所涉及的脉冲电流产生电路中，可选地，所述电流发生器根据所述脉冲电流参数生成低精度脉冲电流或高精度脉冲电流，所述电流发生器在接收所述脉冲电流参数之后，判断所要生成的双向脉冲电流信号是否小于临界值，并且当所要生成的双向脉冲电流信号小于或等于临界值时，生成所述高精度脉冲电流；当所要生成的双向脉冲电流信号大于临界值时，生成所述低精度脉冲电流。由此，电流发生器能够在不同的情形下产生对应的脉冲电流，以满足刺激信号的要求。
另外，在本发明所涉及的脉冲电流产生电路中，可选地，当所述双向脉冲电流信号的所述负向脉冲宽度大于所述预设时长且所述负向脉冲幅度小于或等于所述临界值时，所述电流发生器生成高精度脉冲电流。在这种情况下，更加有效地刺激神经细胞。
另外，在本发明所涉及的脉冲电流产生电路中，可选地，所述高精度脉冲电流的脉冲幅度的精度大于所述低精度脉冲电流的脉冲幅度的精度。由此，电流发生器可以根据实际情形，产生不同精度的脉冲电流，以满足不同神经刺激信号的要求。
另外，在本发明所涉及的脉冲电流产生电路中，可选地，所述双向脉冲电流信号的一个刺激周期内的正向脉冲电流或负向脉冲电流的电荷总量在安全电荷量以内。由此，能够确保刺激电极的长期安全性和可靠性。
此外，本发明的第二方面提供一种电荷补偿电路，其是用于对脉冲电流产生电路进行电荷补偿的电荷补偿电路，所述脉冲电流产生电路产生用于神经刺激的双向脉冲电流，所述电荷补偿电路包括：检测电路，其用于检测由所述脉冲电流产生电路生成的所述双向脉冲电流信号的一个刺激周期内的电荷总量；判断电路，其用于判断由所述检测电路检测的所述电荷总量是否超过安全电荷量；以及补偿电路，其用于当所述判断电路判断所述电荷总量超过安全电荷量时，产生具有净电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。
在本发明的第二方面中，通过检测电路来检测由脉冲电流产生电路所生成的双向脉冲电流信号在一个刺激周期内的电荷总量，利用判断电路来判断由检测电路检测的电荷总量是否超过安全电荷量，并且当判断电路判断电荷总量超过安全电荷量时，补偿电路产生具有净电荷量的补偿脉冲电流信号以使电荷总量在所述安全电荷量以内。如此，在不使用占据面积较大的大电容(RC电路)的情况下，通过发送具有净电荷量的补偿脉冲电流信号对双向脉冲电流进行电荷平衡，由此，能够在有限的空间内充分地提高电荷平衡能力。
另外，在本发明所涉及的电荷补偿电路中，在所述补偿电路中，当所述判断电路判断所述电荷总量为正值时，产生具有负值的补偿电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内，并且当所述判断电路判断所述电荷总量为负值时，产生具有正值的补偿电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。由此，能够更加有效地确保用于神经刺激的电荷总量在安全电荷 量以内。
另外，在本发明所涉及的电荷补偿电路中，可选地，所述补偿脉冲电流信号的幅值低于预设幅值，并且所述补偿脉冲电流信号的周期小于所述双向脉冲电流信号的周期。在这种情况下，可以用多次补偿的方式快速完成电荷补偿。
另外，在本发明所涉及的电荷补偿电路中，可选地，在所述双向脉冲电流信号中，正向脉冲电流信号的波形与负向脉冲电流信号的波形相反，所述检测电路检测所述正向脉冲电流信号的电荷量与所述负向脉冲电流信号的电荷量的绝对值，所述判断电路通过比较所述正向脉冲电流信号的电荷量与所述负向脉冲电流信号的电荷量的绝对值来判断所述电荷总量是否超过安全电荷量。
另外，在本发明所涉及的电荷补偿电路中，可选地，所述检测电路检测由脉冲电流产生电路生成的所述双向脉冲电流信号的平均值，所述判断电路判断所述平均值的绝对值是否大于预设值，并且当所述平均值的绝对值大于所述预设值时，补偿电路产生具有净电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。在这种情况下，通过检测平均值是否大于预设值，能够方便地确定是否需要提供电荷补偿。
另外，在本发明所涉及的电荷补偿电路中，可选地，所述检测电路检测由所述脉冲电流产生电路生成的双向脉冲电流信号的电流平均值，并将所述电流平均值转换为电压平均值，并且所述判断电路判断所述电压平均值的绝对值是否大于预设电压值，当所述电压平均值的绝对值大于所述预设电压值时，所述补偿电路产生具有净电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。在这种情况下，可以将电流平均值转换成电压平均值来检测，并且通过将电压平均值的绝对值与预设电压值相比，当所述电压平均值的绝对值大于所述预设电压值时，通过补偿电路的补偿能够使用于神经刺激的电荷总量在所述安全电荷量以内。
另外，在本发明所涉及的电荷补偿电路中，可选地，当所述电压平均值的绝对值大于预设电压值，且所述电压平均值为正值时，所述补偿电路产生具有负值的净电荷量的补偿脉冲电流信号以使用于神经 刺激的所述电荷总量在所述安全电荷量以内，并且当所述电压平均值的绝对值大于预设电压值，且所述电压平均值为负值时，所述补偿电路产生具有正值的净电荷量的补偿脉冲电流信号以使用于神经刺激的所述电荷总量在所述安全电荷量以内。
另外，在本发明所涉及的电荷补偿电路中，所述预设幅值是能够对神经组织起到刺激作用的最小电流幅值。由此，可以防止补偿脉冲电流信号可能对神经组织产生的误刺激。
另外，本发明的第三方面提供一种电荷补偿方法，其是用于对脉冲电流产生电路进行电荷补偿的电荷补偿方法，所述脉冲电流产生电路产生用于神经刺激的双向脉冲电流，所述电荷补偿方法包括：检测由所述脉冲电流产生电路生成的所述双向脉冲电流信号的一个刺激周期内的电荷总量；判断由所述检测电路检测的所述电荷总量小于或等于安全电荷量；并且当所述判断电路判断所述电荷总量超过安全电荷量时，产生具有净电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。
另外，在本发明所涉及的电荷补偿方法中，可选地，当判断所述电荷总量为正值时，产生具有负值的补偿电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内，并且当判断所述电荷总量为负值时，产生具有正值的补偿电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。由此，能够更加有效地确保用于神经刺激的电荷总量在所述安全电荷量以内。
此外，本发明的第四方面提供一种植入式视网膜电刺激器，其包括：植入装置，其至少具有上述任一项所述的脉冲电流产生电路或电荷补偿电路；摄像装置，其用于捕获视频图像，并且将所述视频图像转换成视觉信号；视频处理装置，其与所述摄像装置连接，并且将所述视觉信号进行处理而生成调制信号；以及模拟信号发射装置，其将所述调制信号发送给所述植入装置，所述植入装置将所接收的所述调制信号转换成作为电刺激信号的所述双向脉冲电流信号，从而对视网膜的神经节细胞或双极细胞发放所述双向脉冲电流信号来产生光感。
根据本发明，能够产生更加有效的刺激效果，而且能够在硬件层面适应更高的处理要求例如刺激算法优化等，并且电荷补偿电路主动 补偿神经组织(例如神经节细胞或双极细胞)上有可能存在的多余的净电荷，能够提高对刺激电荷的电荷平衡的效率，确保神经刺激的安全性和可靠性。另外，能够在不利用占据面积较大的大电容的情况下，在有限的空间内充分地提高电荷平衡能力。
附图说明
图1是示出了本发明的第1实施方式所涉及的植入式视网膜电刺激器的结构示意图；
图2是示出了本发明的第1实施方式所涉及的植入式视网膜电刺激器的刺激电极结构植入到眼球内的示意图；
图3是示出了图2所示的刺激电极结构(刺激端)贴附在眼球内的视网膜上的局部示意图；
图4是示出了本发明的第1实施方式所涉及的用于神经刺激的脉冲电流产生电路的电路模块的示意图；
图5是示出了本发明的第1实施方式所涉及的双向脉冲电流信号的示意图；
图6是示出了本发明的第1实施方式所涉及的电流发生器的电路模块的示意图；
图7是示出了本发明的第1实施方式所涉及的不同脉冲电流幅度的精度的示意图；
图8a～图8d是示出了不同的双向脉冲电流的刺激波形的示意图；
图9是示出了发明的第2实施方式所涉及的脉冲电流产生电路的结构示意图；
图10是示出了本发明的第2实施方式所涉及的电荷补偿电路的结构示意图；
图11是示出了本发明的第2实施方式所涉及的补偿脉冲电流的示意图；
图12是示出了本发明的第2实施方式所涉及的电荷补偿电路的电路结构示意图。
具体实施方式
以下，参考附图，详细地说明本发明的优选实施方式。在下面的说明中，对于相同的部件赋予相同的符号，省略重复的说明。另外，附图只是示意性的图，部件相互之间的尺寸的比例或者部件的形状等可以与实际的不同。
(第1实施方式)
图1是示出了本发明的第1实施方式所涉及的植入式视网膜电刺激器的结构示意图。图2是示出了本发明的第1实施方式所涉及的植入式视网膜电刺激器的刺激电极结构植入到眼球内的示意图。图3是示出了图2所示的刺激电极结构(刺激端)贴附在眼球内的视网膜上的局部示意图。
在本实施方式中，如图1所示，植入式视网膜电刺激器(有时也称“人工视网膜”、“人工视网膜系统”)1可以包括体内植入部分即植入装置10、以及体外部分即体外设备30。在本实施方式所涉及的植入式视网膜电刺激器中，植入装置10与体外设备30可以经由无线方式耦合。在一些示例中，植入装置10与体外设备30可以经由图1所示的接收天线13与发射天线33进行耦合。另外，在本实施方式中，植入装置10与体外设备30的耦合方式不限于此，例如植入装置10与体外设备30也可以经由红外接收的方式来实现。
在一些示例中，植入装置10主要包括基体(未图示)以及设置在基体上的电子封装体11、刺激电极结构12和接收天线13。另外，植入装置10中的基体可以经过例如缝合方式固定在眼球20上。
此外，如图2所示，植入装置10中的刺激电极结构12的刺激端12a(刺激电极阵列)可以经由眼球20的切口进入眼球20的玻璃体腔内，并且贴近于视网膜，以便能够对视网膜(特别是视网膜的神经节细胞或双极细胞)进行电刺激(例如发放双向脉冲电流)(参见图3)。
在一般情况下，例如对于视网膜色素变性(RP)或老年黄斑变性(AMD)等病患者而言，因视网膜色素变性(RP)或老年黄斑变性(AMD)而造成感光细胞的衰退或死亡，也即正常的视觉通路因感光细胞病的病变而受到阻碍，正常进入眼内的光无法被转变成视觉电信号，导致患者丧失视觉。在本实施方式中，刺激电极结构12的刺激端12a相当于替代了感光细胞的作用，刺激端12a通过产生电刺激信号例 如发放双向脉冲电流信号，从而对视网膜神经节细胞或双极细胞进行刺激(参见图3)。由于大部分视网膜色素变性(RP)或老年黄斑变性(AMD)患者除了感光细胞外的其他视觉通路大多得到完好保留，因此，神经节细胞或双极细胞受到由刺激电极结构12产生电刺激信号刺激后，该电刺激信号经由保留完好的下游视觉通路(视神经)传递至大脑皮层并产生光感，从而能够部分恢复病人的视觉。
此外，需要说明的是，尽管本实施方式着眼于植入式视网膜电刺激器的视神经刺激进行描述，然而，本实施方式并不限于人工视网膜领域，相反，本实施方式所涉及的脉冲电流产生电路100也可以适用于其他神经刺激领域例如人工耳蜗、深脑部刺激、心脏起搏器、脊髓刺激器、等。
(体外设备)
在本实施方式中，如图1所示，体外设备30可以包括摄像装置31、视频处理装置32和发射天线33。在体外设备30中，摄像装置31可以用于捕获视频图像，并且将所捕获的视频图像转换成视觉信号。
在一些示例中，摄像装置31可以为具有摄像功能的设备例如摄像机、数字照相机、CCD相机等。通过该摄像装置31，从而能够捕获例如外界的影像。另外，为了方便使用，可以将体积较小的摄像机嵌在眼镜上。另外，也可以通过佩戴轻便的具有摄像功能的眼镜作为摄像装置31来捕获视频图像。再者，摄像装置31也可以用谷歌眼镜
Figure PCTCN2017104678-appb-000001
等来实现。另外，在本实施方式中也可以通过使用超声波成像(例如声呐)或电磁波成像(例如雷达)来获取图像，或者也可以使用其他能够生成范围和角度信息的设备。
如图1所示，视频处理装置32与摄像装置31连接，并且接收由摄像装置31提供的视觉信号。在由摄像装置31捕获的视觉信号传给视频处理装置32之后，视频处理装置32可以对该视觉信号进行处理。在一些示例中，视频处理装置32可以包括微处理器、专用集成电路(ASIC)、DSP等，以便对该视觉信号进行图像处理(例如采样、编码、调制、滤波等)。另外，视频处理装置32还具有供电电源，该供电电源可以例如经由无线传输的方式提供能量信号给的植入装置10，从而使植入在眼球20内的植入装置10得到供电。
模拟信号发射装置(即发射天线33)可以将包含由视频处理装置32提供的能量信号和处理后的视觉信号作为调制信号(例如RF调制信号)发送给人工视网膜的植入装置10。
另一方面，植入装置10可以用于接收由视频处理装置32经由例如发射天线33发射的调制信号，并且将该调制信号进行进一步处理，生成双向脉冲电流作为用于神经刺激的刺激电流(刺激信号)。
具体而言，图1所示的接收天线13(即稍后描述的模拟信号接收装置101的具体实施例)接收该调制信号，并将其传输给后续的电子封装体11进行处理。最后，将由电子封装体11(具体是电子封装体11内的处理电路)根据该调制信号产生电刺激信号并且传送到刺激电极结构12的刺激端12a(例如刺激电极阵列)，从而能够对例如视网膜的神经节细胞或双极细胞进行刺激(参见图3)，神经节细胞或双极细胞接收脉冲电流后产生兴奋响应从而产生光感。在上述情况下，刺激电流有可能刺激到视网膜的神经节细胞或视网膜的双极细胞，也有可能同时刺激到视网膜的神经节细胞或双极细胞。
(脉冲电流产生电路)
图4是示出了本发明的第1实施方式所涉及的用于神经刺激的脉冲电流产生电路的电路模块的示意图。图5是示出了本发明的第1实施方式所涉及的双向脉冲电流信号的示意图。
如图4所示，本实施方式所涉及的用于神经刺激的脉冲电流产生电路100可以包括模拟信号接收装置101、模数转换器102、电流信号控制器103和电流发生器104。
在本实施方式中，脉冲电流产生电路100可以应用于图1所示的植入式视网膜电刺激器。在这种情况下，脉冲电流产生电路100可以位于图1所示的植入装置10内。
在一些示例中，例如在植入装置10中，脉冲电流产生电路100可以产生用于刺激视网膜神经节细胞或双极细胞的双向脉冲电流信号。此外，在一些示例中，通过设置在植入装置10中的刺激电极结构12的刺激端12a(参考图2)，能够将由脉冲电流产生电路100产生的双向脉冲电流信号发放到例如视网膜的神经节细胞或双极细胞。
(模拟信号接收装置)
在本实施方式中，模拟信号接收装置101用于接收模拟信号，可以采用天线的形式。模拟信号接收装置101将所接收的模拟信号传送给模数转换器102。如上所述，模拟信号接收装置101可以是由接收线圈组成的接收天线13。这里，接收天线13的线圈可以由金等金属线绕制而成。另外，接收天线13的线圈的匝数没有特别限制，可以根据需要进行设置。
(模数转换器)
模数转换器102可以将由模拟信号接收装置101所接收的模拟信号转换为数字控制信号，并将数字控制信号传送给电流信号控制器103。在本实施方式中，模数转换器102的电路结构没有特别限制，可以根据需要使用4位、6位、8位、10位、14位、16位等不同分辨率的A/D转换器。另外，模数转换器102可以采用逐次逼近型A/D转换器，也可以采用并联比较型的A/D转换器，还可以采用积分型的A/D转换器。另外，数字控制信号可以是一串数字信号流，其指示了后续所要生成的双向脉冲电流信号的脉冲电流参数。
(电流信号控制器)
电流信号控制器103可以根据由模数转换器102输出的数字控制信号来产生用于生成双向脉冲电流信号的脉冲电流参数。这里，双向脉冲电流作为刺激信号可以包含正向脉冲电流和反向脉冲电流。对于神经刺激领域而言，双向脉冲电流的正向脉冲电流的电荷与反向脉冲电流的电荷一般需要保持相等，以确保对神经组织刺激时的安全性。关于双向脉冲电流对神经刺激的作用稍后更详细描述。
在一些示例中，双向脉冲电流可以采用方波型的双向脉冲电流。在这种情况下，双向脉冲电流的脉冲电流参数可以包括负向脉冲宽度t1、负向脉冲幅度I1、正向脉冲宽度t2、正向脉冲幅度I2、以及脉冲间隔t3(参见图5)。这里，脉冲间隔t3是指负向脉冲与正向脉冲之间的时间间隔。另外，时间T为稍后描述的刺激周期T。
如上所述，电流信号控制器103可以根据数字控制信号产生用于生成双向脉冲电流信号的脉冲电流参数。在一些示例中，数字控制信号可以指示电流控制器103生成负向脉冲宽度t1较宽(例如t1＞t2)的双向脉冲电流。在另一些示例中，数字控制信号可以指示电流控制 器103生成负向脉冲幅度I1较小(例如I1＜I2)的双向脉冲电流。
(电流发生器)
电流发生器104可以根据脉冲电流参数生成用于神经刺激的双向脉冲电流信号。在本实施方式中，由于用于神经刺激的脉冲电流产生电路100能够在增加刺激脉冲电流的宽度的情况下保持脉冲电流的高精度，因此能够提供更有效的电流刺激效果，例如能够有效地刺激到视网膜的双极细胞。另一方面，由于能够实现更宽的脉冲调制范围，因此，能够在硬件层面适应更高的处理要求例如刺激算法优化等。
在本实施方式中，电流发生器104可以根据脉冲电流参数生成至少两种不同精度的脉冲电流。在一些示例中，电流发生器104能够生成两种不同精度的脉冲电流。在另一些示例中，电流发生器104能够生成3种、4种、5种或5种以上的不同精度的脉冲电流。另外，相邻不同脉冲电流之间的不同精度倍数可以为2倍，例如，在电流发生器104生成第1脉冲电流、第2脉冲电流、第3脉冲电流、第4脉冲电流和第5脉冲电流5种不同精度的脉冲电流的情况下，第5脉冲电流的精度是第4脉冲电流精度的2倍，第4脉冲电流的精度是第3脉冲电流的精度的2倍，第3脉冲电流的精度是第2脉冲电流的精度的2倍，第2脉冲电流的精度是第1脉冲电流的精度的2倍。另外，本实施方式并不限于此，也可以采用其他不同精度的脉冲电流。
(阻抗负载)
如图4所示，电流发生器104对神经组织等进行神经刺激时相当于连接了阻抗负载110。例如，在本实施方式所涉及的脉冲电流产生电路100用于人工视网膜的神经刺激时，人体组织液内的视网膜的神经节细胞或双极细胞可以简化地等效为阻抗负载110。
以下，参考图6和图7对本实施方式所涉及的电流发生器104更详细地说明。图6是示出了本发明的第1实施方式所涉及的电流发生器的电路模块的示意图。图7是示出了本发明的第1实施方式所涉及的不同脉冲电流幅度的精度的示意图。图8a～图8d是示出了不同的双向脉冲电流的刺激波形的示意图
如图6所示，电流发生器104可以包括N个电流源。在一些示例中，N个电流源可以由1个基准电流源1041、以及(N-1)个镜像电流 源(电流源阵列)构成，这些电流源例如分别受开关S1、开关S2、……、开关S(N)控制。这里，开关S1、开关S2、……、开关S(N)控制电流发生器104所产生的总脉冲电流的幅度大小，也即，总的脉冲电流的脉冲幅度(正向或负向脉冲幅度)与闭合的开关S(N)数目成正比。其中，开关S1控制基准电流源1041。在这种情况下，电流发生器104所产生的总的电流幅度Itotal＝(闭合开关的数目+1)×基准电流源的电流幅度。
在电流发生器104由上述N个电流源组成的情况下，脉冲电流的大小可以由(N+1)个电流源的开闭来确定，并且该脉冲电流的精度可以由基准电流源1041的大小决定。具体而言，基准电流源1041的大小即为脉冲电流精度的大小。例如，如果基准电流源1041的大小为1μA(微安)，则脉冲电流精度为1μA，(N-1)个镜像电流源即电流源1042、电流源1043、……电流源104(N)中各个镜像电流源的电流值均与基准电流源1041的电流值相同。当基准电流源1041的大小设定好之后，电流源1042、电流源1043、……、电流源104(N)中的各个镜像电流源的电流值与基准电流源1041相等。
在一些示例中，如果基准电流源1041和(N-1)个镜像电流源的个数总共为N＝512个，并且设置基准电流源1041的精度为1μA，则电流发生器104可以生成精度为1μA的具有512种脉冲幅度的脉冲电流，也即，通过控制开关S1、开关S2、……、开关S(N)，电流发生器104可以生成1μA、2μA、3μA、……、512μA共512种不同的电流幅度。在另外一些示例中，如果基准电流源1041和(N-1)个镜像电流源的个数总共为N＝512个，并且设置基准电流源1041的精度为4μA，则电流发生器104可以生成精度为4μA的具有128种脉冲幅度的脉冲电流，也即，通过控制开关S1、开关S2、……、开关S(N)，电流发生器104可以生成4μA、8μA、12μA、...512μA总共128种不同的电流幅度。在其他一些示例中，如果基准电流源1041和(N-1)个镜像电流源的个数总共为N＝512个，并且设置基准电流源1041的精度为8μA，则电流发生器104可以生成精度为8μA的具有64种脉冲幅度的脉冲电流也即，通过控制开关S1、开关S2、……、开关S(N)，电流发生器104可以生成8μA、16μA、24μA、...512μA共64种不同的电流幅度。尽管在上述 的描述中以电流精度为1μA、4μA和8μA作为示例进行介绍，但本实施方式并不限于此，本实施方式所涉及的脉冲电流产生电路100也可以生成例如2μA、6μA、12μA等其他精度的电流。
如上所述，由于可以通过设置不同电流大小的基准电流源1041来实现不同的电流精度，因此，在本实施方式中，能够通过设置多种不同的基准电流源来设置所生成的脉冲电流的精度，从而能够生成多种不同精度的脉冲电流。在本实施方式中，可以设置两种不同基准电流源，在这种情况下，可以实现两种不同精度(高精度和低精度)的脉冲电流。
在一些示例中，电流发生器104可以生成第1脉冲幅度精度(高精度)和第2脉冲幅度精度(低精度)两种不同精度的双向脉冲电流。例如可以令第1脉冲幅度精度为1μA/步(step)，电流幅度的范围为0～8μA；令第2脉冲幅度精度为8μA/步，电流幅度的范围为8～512μA(参见图7)。这里，高精度脉冲电流的脉冲幅度的精度(第1脉冲幅度精度1μA/步)大于低精度脉冲电流的脉冲幅度的精度(第2脉冲幅度精度为8μA/步)。由此，电流发生器104可以根据实际情形，产生不同精度的脉冲电流，以满足不同神经刺激信号的要求。另外，在其他一些示例中，电流发生器104能够提供更多不同精度的脉冲电流。
(双向脉冲电流信号)
在一些示例中，由电流产生器104生成的双向脉冲电流信号的一个刺激周期T内的电荷总量在安全电荷量以内(例如电荷总量为零)。具体而言，在神经刺激领域中，为了防止脉冲电流信号对人体神经组织例如视网膜的神经节细胞或双极细胞产生净电荷而对人体神经组织造成伤害，需要保证双向脉冲电流信号在一个刺激周期T内的电荷总量在安全电荷量以内。
这里，“安全电荷量”是神经组织(例如视网膜的神经节细胞或双极细胞)在安全范围内所能承受净电荷的最大值。超过该安全电荷量的净电荷有可能会对神经组织造成损伤。这里，一个刺激周期T为产生一次刺激信号的周期时间。因此，在实际的神经刺激过程中，需要保证将一个刺激周期T内的电荷总量控制在所述安全电荷量以内。这里，一个刺激周期T为产生一次刺激信号的周期时间。电荷总量是指 双向脉冲电流信号的一个刺激周期T内的净电荷的电荷总量。在一些示例中，为了方便起见，也可以令安全电荷量为零。
另外，在本实施方式中，只要确保双向脉冲电流在一个刺激周期T内的电荷总量在安全电荷量以内即可，并不限定脉冲电流的波形。图8a～图8d示出了不同的双向脉冲电流的刺激波形的示意图。由于在神经刺激领域中，负向脉冲电流通常作为有效刺激信号，因此，在图8a～图8d中，以负向脉冲波形为例，列举了双向脉冲电流信号的变形例。
如图8a～图8d所示，作为刺激波形的双向脉冲电流信号，尽管其负向脉冲的波形和正向脉冲的波形并不一定相同，但是只要保证该双向脉冲电流信号在一个刺激周期T内的电荷总量在安全电荷量以内即可。作为例子，负向脉冲宽度t11、t12、t13和t14可以均大于正向脉冲宽度t2，由此可以实现宽的刺激脉冲。另外，双向脉冲电流可以是双向方波脉冲电流信号，也可以是余弦脉冲电流信号，还可以是方波与余弦脉冲电流信号的组合。
如上所述，电流发生器104可以根据脉冲电流参数生成双向脉冲电流信号。具体而言，该双向脉冲电流信号可以包括有效刺激电流信号和平衡电流信号。其中，有效刺激电流信号是对神经刺激对象例如神经节细胞或双极细胞有刺激作用的电流信号；平衡电流信号是用于平衡有效刺激电流信号所产生的电荷的电流信号。一般而言，若有效刺激信号为正向脉冲，则平衡电流信号为负向脉冲；若有效刺激信号为负向脉冲，则平衡电流信号为正向脉冲。由此，能够确保在一个刺激周期T内双向脉冲电流信号的电荷总量在安全电荷量以内。(例如该电荷总量为零)。
在本实施方式中，如上所述，电流信号控制器103产生用于生成双向脉冲电流信号的脉冲电流参数。由此，可以通过设置脉冲电流参数来使电流发生器104理论上产生的双向脉冲电流信号在一个刺激周期内的电荷总量在安全电荷量以内。另外，为了抑制刺激电流信号可能积累的净电荷对人体造成的影响，双向脉冲电流信号通常被设置成正向脉冲和负向脉冲中只有一个是刺激信号，另外一个是平衡电流信号，由此，确保在一个刺激周期T内的双向脉冲电流信号的电荷总量在安全电荷量以内。
作为具体例子，在一个刺激周期T内，双向脉冲电流信号的负向脉冲信号在时间上的积分可以与双向脉冲电流信号的正向脉冲信号在时间上的积分的绝对值相等，由此，在一个刺激周期T内的双向脉冲电流信号的电荷总量在安全电荷量以内。另外，再参考图5，如图5所示，在一个刺激周期T内，负向脉冲信号的持续时长(负向脉冲宽度)为t1，正向脉冲信号的持续时长(正向脉冲宽度)为t2，则负向脉冲在t1时长内的积分的绝对值与正向脉冲在t2时长内的积分的绝对值相等，即双向脉冲电流信号的电荷总量在安全电荷量以内(例如该电荷总量为零)。
如上所述，电流发生器104提供了两种不同的脉冲幅度精度，第1脉冲幅度精度和第2脉冲幅度精度，其中，第1脉冲幅度精度为1μA/步，幅度范围为0～8μA(例如1μA、2μA、3μA、……、8μA)；第2脉冲幅度精度为8μA/步，幅度范围为8～512μA(例如8μA、16μA、24μA、……、512μA)(参见图7)。
在一些示例中，如图7所示，当神经刺激对象例如视网膜的神经节细胞或双极细胞需要较低的脉冲电流刺激时，电流发生器104可以提供精度较高的脉冲幅度精度(例如1μA/步)，例如当神经节细胞或双极细胞需要的电流幅度小于或等于8μA时，生成脉冲幅度精度为1μA/步的电流，可以提供1μA、2μA、3μA、4μA、5μA、6μA、7μA、8μA共8种脉冲幅度的电流；当神经节细胞或双极细胞需要的电流大于8μA时，生成脉冲幅度精度为8μA/步的电流，可以提供16μA、24μA、32μA、40μA、...512μA共64种脉冲幅度的电流。
在本实施方式中，电流发生器104能够提供至少两种不同的精度的脉冲幅度，生成至少两种不同精度的脉冲电流，由此能够提供更高效的电流刺激方式。
在一些示例中，电流发生器104可以根据脉冲电流参数生成低精度脉冲电流或高精度脉冲电流。具体而言，电流发生器104在接收脉冲电流参数之后，判断所要生成的双向脉冲电流信号的脉冲幅度是否小于临界值。当所要生成的双向脉冲电流信号的脉冲幅度小于或等于临界值时，电流发生器104生成高精度脉冲电流；当所要生成的双向脉冲电流信号的脉冲幅度大于临界值时，电流发生器104生成低精度 脉冲电流。由此，电流发生器104能够在不同的情形下产生对应的脉冲电流，以满足不同神经刺激信号的要求。
在本实施方式中，临界值可以预先进行设定。另外，高精度脉冲电流的幅度精度和低精度脉冲电流的幅度精度也可以预先进行设定。例如，如图7所示，临界值可以设置为8μA，高精度脉冲电流的幅度精度为1μA/步，低精度脉冲电流的幅度精度为8μA/步。
在这种情况下，当电流发生器104判断所要生成的双向脉冲电流信号的幅度小于或等于8μA时，电流发生器104生成高精度(1μA/步)脉冲电流；当电流发生器104判断所要生成的双向脉冲电流信号的幅度大于8μA时，电流发生器104生成低精度(8μA/步)脉冲电流。如此，电流发生器104可以提供两种不同精度的脉冲电流，当神经节细胞或双极细胞需要的脉冲电流较小时，提供高精度的脉冲电流，可以更加准确的刺激到视网膜的双极细胞，能够提供更加高效的刺激方式。
在一些示例中，当双向脉冲电流信号的正向脉冲宽度大于预设时长且正向脉冲幅度小于临界值时，或者当双向脉冲电流信号的负向脉冲宽度大于预设时长且负向脉冲幅度小于临界值时，电流发生器104产生高精度脉冲电流。
对于刺激脉冲电流的宽度(刺激时间)，尽管作用机理目前仍未完全明确，但是通过延长刺激脉冲宽度(例如负向脉冲宽度)，更有可能刺激到更深入的神经细胞，由此能够获得更加有效的神经刺激。例如对于植入式视网膜电刺激器而言，宽的刺激脉冲能够更有效地刺激到视网膜的双极细胞，由此能够提供更有效和更精准的神经刺激。
具体而言，当双向脉冲电流信号的负向脉冲宽度大于预设时长且负向脉冲幅度小于临界值时，该双向脉冲电流信号能够更加精准的刺激到视网膜的双极细胞，由于双极细胞在视觉通路上的一一对应性比神经节细胞优越，因此精准的刺激双极细胞可以形成更加准确的光感。另外，也能够在硬件层面适应更高的处理要求例如刺激算法优化等。
如此，当双向脉冲电流信号的正向脉冲宽度大于预设时长且正向脉冲幅度小于临界值时，或者当双向脉冲电流信号的负向脉冲宽度大于预设时长且负向脉冲幅度小于临界值时，电流发生器104产生高精 度脉冲电流，精准的刺激双极细胞，形成更加准确的光感，可以给盲人提供更加高效的刺激方式。
(第2实施方式)
图9是示出了本发明的第2实施方式所涉及的脉冲电流产生电路的电路结构示意图。图10是示出了本发明的第2实施方式所涉及的电荷补偿电路的电路结构示意图。图11是示出了本发明的第2实施方式所涉及的补偿脉冲电流的示意图。图12是示出了本发明的第2实施方式所涉及的电荷补偿电路的电路结构示意图。
第2实施方式所涉及脉冲电流产生电路200与第1实施方式所涉及的脉冲电流产生电流100的不同点在于，除了包括第1实施方式的模拟信号接收装置101、模数转换器102、电流信号控制器103和电流发生器104之外，还包括电荷补偿电路106。
此外，需要说明的是，尽管本实施方式着眼于植入式视网膜电刺激器的视神经刺激进行描述，然而，本实施方式并不限于人工视网膜领域，相反，本实施方式所涉及的电荷补偿电路106也可以适用于其他神经刺激领域例如人工耳蜗、深脑部刺激、心脏起搏器、脊髓刺激器、等。
如图9所示，本实施方式所涉及的用于神经刺激的电荷补偿电路106。在本实施方式中，电荷补偿电路106可以应用于图1所示的植入式视网膜电刺激器。在这种情况下，电荷补偿电路106可以位于图1所示的植入装置10内(例如电子封装体11内)。具体而言，脉冲电流产生电路200可以位于图1所示的电子封装体11。在本实施方式中，电荷补偿电路106可以用于对脉冲电流产生电路200进行电荷补偿。
在本实施方式中，如图10所示，电荷补偿电路(也可以称“主动电荷补偿电路”)106包括检测电路1061、判断电路1062和补偿电路1063。检测电路1061可以用于检测由脉冲电流产生电路200生成的双向脉冲电流信号的一个刺激周期T内的电荷总量。
另外，判断电路1062可以用于判断由检测电路1061检测的电荷总量是否超过安全电荷量。此外，补偿电路1063可以用于当判断电路1062判断电荷总量超过安全电荷量时，产生具有净电荷量的补偿脉冲电流信号以使用于神经刺激的电荷总量在所述安全电荷量以内。这里， 净电荷量根据需要补偿的情况，可以为负电荷的电荷量，也可以为正电荷的电荷量。
理论上，可以通过设置双向脉冲电流信号的脉冲电流参数(例如，脉冲电流参数可以包括正向脉冲宽度、正向脉冲幅度、负向脉冲宽度、负向脉冲幅度、脉冲间隔等)而使得双向脉冲电流信号在一个刺激周期T内的电荷总量在所述安全电荷量以内。然而，在实际应用电路中，脉冲电流产生电路200所生成的双向脉冲电流信号因为各种因素在一个刺激周期T内的电荷总量很可能会超出安全电荷量。在这种情况下，双向脉冲电流信号所积累的净电荷有可能对人体眼部神经节细胞或双极细胞会造成损害。
在本实施方式中，通过电荷补偿电路106来主动补偿神经组织(例如神经节细胞或双极细胞)上积累的多余的净电荷，能够提高对刺激电荷的电荷平衡能力，确保神经刺激的安全性和可靠性。由此起到保护人体神经组织例如视网膜神经节细胞或双极细胞的作用。
在本实施方式中，检测电路1061可以用于检测脉冲电流产生电路200生成的双向脉冲电流信号的一个刺激周期T内的电荷总量。接着，判断电路1062判断由检测电路1061检测的双向脉冲电流信号的一个刺激周期T内的电荷总量是否超过安全电荷量。如果双向脉冲电流信号的一个刺激周期T内的电荷总量在安全电荷量以内，则补偿电路1063不工作；如果双向脉冲电流信号的一个刺激周期T内的电荷总量超过安全电荷量，则补偿电路1063产生具有净电荷量的补偿脉冲电流信号，使得用于神经刺激的电荷总量在所述安全电荷量以内。
具体而言，当判断电路1062判断双向脉冲电流信号在一个刺激周期T内的电荷总量为正电荷时，补偿电路1063产生负向电流脉冲，以使用于神经刺激的电荷总量在所述安全电荷量以内；当判断电路1062判断双向脉冲电流信号在一个刺激周期T内的电荷总量为负电荷时，补偿电路1063产生正向电流脉冲，以使用于神经刺激的电荷总量在所述安全电荷量以内。
在本实施方式中，补偿电路1063可以主动进行电荷补偿。一旦判断电路1062判断由检测电路1061检测的脉冲电流产生电路200所产生的一个刺激周期内的电荷总量超过安全电荷量，因此补偿电路1063 可以及时进行电荷补偿，提高电荷平衡效率或能力，确保被刺激的神经组织的安全性。
在一些示例中，当判断电路1062判断双向脉冲电流信号的一个刺激周期T内的电荷总量超过安全电荷量时，补偿电路1063可以产生具有净电荷量的补偿脉冲电流信号，使得用于神经刺激的电荷总量在所述安全电荷量以内。另外，当判断电路1062判断双向脉冲电流信号的一个刺激周期T内的电荷总量小于零时，补偿电路1063可以产生具有正值的净电荷量的补偿脉冲电流信号使得用于神经刺激的电荷总量在所述安全电荷量以内。
例如，当判断电路1062判断双向脉冲电流信号的一个刺激周期T内的电荷总量为-1×10-7库伦的负电荷时，补偿电路1063产生电荷总量为1×10-7库伦的正电荷(例如，补偿电路1063可以产生一个脉冲宽度为1毫秒、脉冲幅值为100微安的正向脉冲，或者补偿电路1063可以产生一个脉冲宽度为10毫秒，脉冲幅值为10微安的正向脉冲)，使得用于神经刺激的电荷总量在安全电荷量以内。又例如，当判断电路1062判断双向脉冲电流信号的一个刺激周期T内的电荷总量为1×10-7库伦的正电荷时，补偿电路1063产生电荷总量为-1×10-7库伦的负电荷(例如，补偿电路1063可以产生一个脉冲宽度为1毫秒，脉冲幅值为100微安的负向脉冲，或者补偿电路1063可以产生一个脉冲宽度为10毫秒，脉冲幅值为10微安的负向脉冲)，使得用于神经刺激的所述电荷总量在所述安全电荷量以内。
在本实施方式中，补偿脉冲电流信号的幅值可以低于预设幅值，并且补偿脉冲电流信号的周期可以小于双向脉冲电流信号的周期。这里，预设幅值是能够对神经组织(例如神经节细胞或双极细胞)起到刺激作用的最小电流幅值，通过将补偿脉冲电流信号的幅值设置为低于预设幅值，由此可以防止补偿脉冲电流信号可能对神经组织(例如神经节细胞或双极细胞)产生的误刺激，抑制神经组织(例如神经节细胞或双极细胞)可能接收到补偿脉冲电流信号而产生不必要的兴奋。另外，也可以设置补偿脉冲电流信号的周期小于双向脉冲电流信号的周期。由此，可以在较短的时间内进行电荷补偿，可以例如用多次补偿的方式快速进行电荷补偿。
在一些示例中，双向脉冲电流信号中的正向脉冲电流信号的波形可以与负向脉冲电流信号的波形相反。也即，在双向脉冲电流信号中，正向脉冲电流信号的波形除了与负向脉冲电流信号反相外，脉冲电流的波形形状相同。如此，检测电路1061可以检测正向脉冲电流信号的电荷量与负向脉冲电流信号的电荷量的绝对值。然后，判断电路1062通过比较正向脉冲电流信号的电荷量与负向脉冲电流信号的电荷量的绝对值来判断电荷总量是否超过安全电荷量。
再参考图5，图5示出了本发明的实施方式所涉及的双向脉冲电流信号的示意图。如图5所示，双向脉冲电流信号可以包括正向脉冲信号和负向脉冲信号，并且正向脉冲电流信号的波形与负向脉冲电流信号的波形相反。此时，检测电路1061可以检测正向脉冲电流信号的电荷量与负向脉冲电流信号的电荷量的绝对值。例如，正向脉冲电流信号的电荷量为Q1＝I1×t1，负向脉冲电流信号的电荷量的绝对值为Q2＝|I2×t2|，|I2×t2|即I2×t2的绝对值。接着，判断电路1062判断电荷量Q1与电荷量Q2之间的差值即净电荷总量＝Q1-Q2。当电荷量Q1与电荷量Q2相等时，则确定电荷总量为零。当电荷量Q1与电荷量Q2不相等时，则确定电荷总量不为零，其中，当电荷量Q1大于电荷量Q2时，确定电荷总量为正值(存在净正电荷)，当电荷量Q1小于电荷量Q2时，确定电荷总量为负值(存在净负电荷)。另外，只要确保上述电荷总量不论是净正电荷或净负电荷在安全电荷量以内即可。
在一些示例中，检测电路1061可以检测由脉冲电流产生电路200生成的双向脉冲电流信号的平均值。具体而言，通过直接计算双向脉冲电流信号的负电荷量与正电荷量之间的净电荷量，并且对该净电荷量取平均值，由此可以获得由脉冲电流产生电路200所生成的双向脉冲电流信号的电荷总量是否存在净电荷。然后，判断电路1062可以判断平均值的绝对值是否大于预设值，并且当平均值的绝对值大于预设值时，补偿电路1063可以产生具有净电荷量的补偿脉冲电流信号以使用于神经刺激的电荷总量在安全电荷量以内。
在本实施方式中，双向脉冲电流信号的平均值可以是双向脉冲电流信号的平均电流值、平均电荷值等。另外，预设值可以是预设电流值、预设电荷值等。
在一些示例中，双向脉冲电流信号的平均值可以是双向脉冲电流信号的平均电流值。在这种情况下，检测电路1061可以检测双向脉冲电流信号的平均电流值为Ia＝|(I1×t1+I2×t2)/(t1+t2)|，其中I2为负值。令预设电流值为I’(I’>0)，判断电路1062可以判断Ia是否大于I’。如果Ia大于I’，则补偿电路1063产生具有净电荷量的补偿脉冲电流信号使得用于神经刺激的电荷总量在安全电荷量以内；如果Ia小于或等于I’，则补偿电路1063不工作。
在一些示例中，双向脉冲电流信号的平均值可以是双向脉冲电流信号的平均电荷值。在这种情况下，检测电路1061可以检测双向脉冲电流信号的平均电荷值为Qa＝|(I1×t1+I2×t2)/2|，其中I2为负值。令预设电荷值为Q’(Q’>0)，判断电路1062可以判断Qa是否大于Q’。如果Qa大于Q’，则补偿电路1063产生具有净电荷量的补偿脉冲电流信号以使用于神经刺激的电荷总量在安全电荷量以内；如果Qa小于或等于Q’，则补偿电路1063不工作。
在一些示例中，检测电路1061可以检测由脉冲电流产生电路200生成的双向脉冲电流信号的电流平均值，并将电流平均值转换为电压平均值。在这种情况下，判断电路1062可以判断该电压平均值的绝对值是否大于预设电压值。在这种情况下，当电压平均值的绝对值大于预设电压值时，补偿电路1063可以产生具有净电荷量的补偿脉冲电流信号以使用于神经刺激的电荷总量在安全电荷量以内。
例如，可以通过电流电压转换电路将电流平均值转换为电压平均值，并且令预设电压值为安全的电压值，当电压平均值低于预设电压值时，表明脉冲电流产生电路200生成的双向脉冲电流信号对人体的神经节细胞或双极细胞没有伤害(没有超出安全电荷量)，补偿电路1063可以不需要进行电荷补偿；当电压平均值高于预设电压值时，表明脉冲电流产生电路200生成的双向脉冲电流信号对人体的神经节细胞或双极细胞可能会产生伤害，则补偿电路1063产生具有净电荷量的补偿脉冲电流信号以使用于神经刺激的电荷总量在安全电荷量以内。
在本实施方式中，可以通过检测电路1061将检测的电流平均值转换为判断电路1062容易进行判断(例如，判断电路1062可以使用电压比较器即可以进行判断)的电压平均值，可以方便判断电路1062判 断是否需要补偿电路1063进行电荷补偿，并且可以提高判断电路1062的判断结果的准确性。
另外，在一些示例中，当电压平均值的绝对值大于预设电压值，且电压平均值为正值时，补偿电路1063可以产生具有负值的净电荷量的补偿脉冲电流信号以使用于神经刺激的电荷总量在安全电荷量以内；当电压平均值的绝对值大于预设电压值，且电压平均值为负值时，补偿电路1063产生具有正值的净电荷量的补偿脉冲电流信号以使用于神经刺激的电荷总量在安全电荷量以内。
在本实施方式中，检测电路1061可以检测由脉冲电流产生电路200生成的双向脉冲电流信号的电流平均值，并将电流平均值转换为电压平均值。判断电路1062可以判断电压平均值的绝对值是否大于预设电压值，当电压平均值的绝对值大于预设电压值时，且电压平均值为正值时，补偿电路1063产生具有负值的净电荷量的补偿脉冲电流信号以使用于神经刺激的电荷总量在安全电荷量以内；当电压平均值的绝对值大于预设电压值时，且电压平均值为负值时，补偿电路1063产生具有正值的净电荷量的补偿脉冲电流信号以使用于神经刺激的电荷总量在安全电荷量以内。
举例来说，若预设电压值为5毫伏(mv)，当电压平均值为大于5毫伏时(即电压平均值的绝对值大于预设电压值时，且电压平均值为正值时)，补偿电路1063产生具有负值的净电荷量的补偿脉冲电流信号以使用于神经刺激的电荷总量在安全电荷量以内，例如，补偿电路1063产生的补偿脉冲电流信号为负向脉冲。另外，当电压平均值为小于-5毫伏时(即电压平均值的绝对值大于预设电压值时，且电压平均值为负值时)，补偿电路1063产生具有正值的净电荷量的补偿脉冲电流信号以使用于神经刺激的电荷总量在安全电荷量以内，例如，补偿电路1063产生的补偿脉冲电流信号为正向脉冲。
图11是示出了本发明的实施方式所涉及的电荷补偿电路的电路结构示意图。如图11所示，电荷补偿电路106可以包括检测电路1061、判断电路1062和补偿电路1063。在本实施方式中，检测电路1061可以具体包括第1电阻R1、第2电阻R2和电容C1。其中，第1电容的负极与第1电阻R1的第1端接入公共电压VSS，第1电容的正极与第 1电阻R1的第2端电连接第2电阻R2的第2端，第2电阻R2的第1端电连接脉冲电流产生电路200和补偿电路1063。
另外，判断电路1062可以具体包括第1电压比较器U1和第2电压比较器U2。其中，第1电压比较器U1的同相输入端和第2电压比较器U2的同相输入端电连接第2电阻R2的第1端，第1电压比较器U1的反相输入端接入预设正电压VTH+，第2电压比较器U2的反相输入端接入预设负电压VTH-，第1电压比较器U1的供电端与第2比较器U2的供电端均接入电源电压VDD，第1电压比较器U1的接地端与第2比较器U2的接地端均接入公共电压VSS，第1电压比较器U1的输出端Out1电连接补偿电路1063的第1控制端C+，第2电压比较器U2的输出端Out2电连接补偿电路1063的第2控制端C-，补偿电路1063的供电端接入电源电压VDD，补偿电路1063的接地端接入公共电压VSS，补偿电路1063的输出端连接脉冲电流产生电路200的输入端，脉冲电流产生电路200的供电端接入电源电压VDD，脉冲电流产生电路200的接地端接入公共电压VSS，脉冲电流产生电路200的输出端连接阻抗负载110。
另外，检测电路1061可以检测脉冲电流产生电路200生成的双向脉冲电流信号在一个刺激周期T内的电荷总量与一个刺激周期T内的电流平均值，并将一个刺激周期T内的电流平均值转换为电压平均值。判断电路1062可以判断上述电压平均值是否位于预设正电压VTH+与预设负电压VTH-之间，如果上述电压平均值位于预设正电压VTH+与预设负电压VTH-之间，则补偿电路1063不需要进行电荷补偿；如果上述电压平均值不位于预设正电压VTH+与预设负电压VTH-之间，则补偿电路1063进行电荷补偿，产生具有净电荷量的补偿脉冲电流信号，以使用于神经刺激的电荷总量在安全电荷量以内。
在本实施方式中，检测电路1061可以用于检测由电流发生器104生成的双向脉冲电流信号在一个刺激周期T内的电荷总量。在一些示例中，检测电路1061可以由积分电路构成。该积分电路可以对由电流发生器104生成的双向脉冲电流信号在一个刺激周期T内的电荷进行积分，由此获得双向脉冲电流信号在一个刺激周期T内的电荷总量。
作为具体例子，假设脉冲电流产生电路200所生成的双向脉冲电 流信号在一个刺激周期T内(例如，周期为1秒)的电荷总量的绝对值超过5×10-7库伦时，则补偿电路1063进行电荷补偿。也即，当双向脉冲电流信号的电流平均值大于5×10-7毫安或者小于-5×10-7毫安时，补偿电路1063进行电荷补偿。如果第2电阻R2的阻值为10千欧，则可以令预设正电压VTH+为5毫伏，预设负电压VTH-为-5毫伏。当判断电路1062判断上述电压平均值超过5毫伏时，第1电压比较器U1的输出端Out1输出高电平，第2电压比较器U2的输出端Out2输出高电平；当判断电路1062判断上述电压平均值低于-5毫伏时，第1电压比较器U1的输出端Out1输出低电平，第2电压比较器U2的输出端Out2输出低电平；当判断电路1062判断上述电压平均值位于-5毫伏～5毫伏之间时，第1电压比较器U1的输出端Out1输出低电平，第2电压比较器U2的输出端Out2输出高电平。
在本实施方式中，补偿电路1063的输出端输出的补偿脉冲电流信号与补偿电路1063的第1控制端C+和补偿电路1063的第2控制端C-相关，请参阅下表1。
表1
第1控制端C+ 第2控制端C- 补偿脉冲电流信号
高电平 高电平 负向脉冲
低电平 低电平 正向脉冲
低电平 高电平 无
当判断电路1062判断上述电压平均值超过5毫伏时，补偿电路1063需要补偿负向脉冲，此时，第1电压比较器U1的输出端Out1输出高电平，第2电压比较器U2的输出端Out2输出高电平，即第1控制端C+为高电平，第2控制端C-为高电平，如表1所示，补偿电路1063生成的补偿脉冲电流信号为负向脉冲。
另外，当判断电路1062判断上述电压平均值低于-5毫伏时，补偿电路1063需要补偿正向脉冲，此时，第1电压比较器U1的输出端Out1输出低电平，第2电压比较器U2的输出端Out2输出低电平，即第1控制端C+为低电平，第2控制端C-为低电平，如表1所示，补偿电路1063生成的补偿脉冲电流信号为正向脉冲。
此外，当判断电路1062判断上述电压平均值位于-5毫伏～5毫伏之间时，补偿电路1063无需进行电荷补偿，第1电压比较器U1的输出端Out1输出低电平，第2电压比较器U2的输出端Out2输出高电平，即第1控制端C+为低电平，第2控制端C-为高电平，如表1所示，补偿电路1063不进行电荷补偿。
在本实施方式中，图11仅仅是本发明的优选实施方式所涉及的一种具体的电荷补偿电路，本实施方式并不限于此。在电荷补偿电路106中，检测电路1061、判断电路1062和补偿电路1063的具体实现方式可以有多种变形。
另外，本实施方式所涉及的电荷补偿方法是用于对脉冲电流产生电路200进行电荷补偿的电荷补偿方法，脉冲电流产生电路200产生用于神经刺激的双向脉冲电流，电荷补偿方法包括：检测由脉冲电流产生电路200生成的双向脉冲电流信号的一个刺激周期内的电荷总量；判断由检测电路1061检测的电荷总量小于或等于安全电荷量；并且当判断电路1062判断电荷总量超过安全电荷量时，产生具有净电荷量的补偿脉冲电流信号以使电荷总量在安全电荷量以内。
另外，在电荷补偿方法中，当判断电荷总量为正值时，产生具有负值的补偿电荷量的补偿脉冲电流信号以使电荷总量在安全电荷量以内，并且当判断电荷总量为负值时，产生具有正值的补偿电荷量的补偿脉冲电流信号以使电荷总量在安全电荷量以内。由此，能够更加有效地确保用于神经刺激的电荷总量在安全电荷量以内。
在一些示例中，当判断电路1062判断双向脉冲电流信号在一个刺激周期T内的电荷总量为正时，补偿电路1063对由电流发生器104生成的双向脉冲电流信号进行负电荷补偿；当判断电路1062判断双向脉冲电流信号在一个刺激周期T内的电荷总量为负电荷时，补偿电路1063可以产生正向电流脉冲对由电流发生器104生成的双向脉冲电流信号进行正电荷补偿。在上述电荷补偿过程中，补偿电路1063优选可以采用逐次逼近电荷补偿方法，由此可以逐步进行电荷补偿，提高电荷补偿的精确性。例如，补偿电路1063可以生成小电流脉冲，对由电流发生器104生成的双向脉冲电流信号进行多次电荷补偿。这里，由补偿电路1063生成的小电流脉冲的净电荷量可以为正或者为负。
另外，在一个优选的实施方式中，可以用电荷收敛补偿方法逐步进行电荷补偿，提高电荷补偿的精确性。在一些示例中，检测电路1061可以检测脉冲电流产生电路200生成的双向脉冲电流信号在一个刺激周期T内的电荷总量。判断电路1062可以判断双向脉冲电流信号在一个刺激周期T内的电荷总量的绝对值是否大于安全电荷量，当判断电路1062判断双向脉冲电流信号在一个刺激周期T内的电荷总量的绝对值超过安全电荷量时，补偿电路1063进行部分电荷补偿。例如，当判断电路1062判断双向脉冲电流信号在一个刺激周期T内的电荷总量为Q1，且Q1的绝对值>Qs(Qs为安全电荷量)时，补偿电路1063进行部分电荷补偿。这里的部分电荷补偿可以为比例电荷补偿，例如按照30％、40％、50％、60％、70％、80％等比例值进行电荷补偿。
例如，假设安全电荷量为5×10-8库伦，当判断电路1062判断双向脉冲电流信号在一个刺激周期T内的电荷总量为1×10-7库伦的负电荷时，补偿电路1063可以按照50％的比例进行正电荷补偿，即补偿电路1063可以进行5×10-8库伦的正电荷补偿。然后，检测电路1061可以继续检测脉冲电流产生电路200累计产生的电荷总量，若判断电路1062判断脉冲电流产生电路200累计产生的电荷总量为6×10-8库伦的负电荷，补偿电路1063进行3×10-8库伦的正电荷补偿。之后，检测电路1061继续检测脉冲电流产生电路200累计产生的电荷总量，当判断电路1062判断脉冲电流产生电路200累计产生的电荷总量超过安全电荷量(5×10-8)时，补偿电路1063继续按照50％的比例进行电荷补偿，直至当判断电路1062判断脉冲电流产生电路200累计产生的电荷总量的绝对值在安全电荷量以内时，补偿电路1063停止进行电荷补偿。当然，在补偿电路1063停止进行电荷补偿之后，检测电路1061可以继续检测脉冲电流产生电路200累计产生的电荷总量，也即是说，检测电路1061可以是一直处于工作状态，实时地进行检测，一旦检测出电荷量超标(脉冲电流产生电路200累计产生的电荷总量的绝对值大于安全电荷量)，补偿电路1063即可进行电荷补偿。
在一些示例中，检测电路1061可以检测脉冲电流产生电路200生成的双向脉冲电流信号在一个刺激周期T内的电荷总量。判断电路1062可以判断双向脉冲电流信号在一个刺激周期T内的电荷总量是否 超过安全电荷量。当判断电路1062判断双向脉冲电流信号在一个刺激周期T内的电荷总量超过安全电荷量时，补偿电路1063可以进行部分电荷补偿。例如，当判断电路1062判断双向脉冲电流信号在一个刺激周期T内的电荷总量为Q1，且Q1超过安全电荷量时，补偿电路1063可以进行部分电荷补偿，这里的部分电荷补偿可以为比例电荷补偿，例如按照30％、40％、50％、60％、70％、80％等比例值进行电荷补偿。
例如，当判断电路1062判断双向脉冲电流信号在一个刺激周期T内的电荷总量为1×10-7库伦的正电荷时，可以按照50％的比例进行正电荷补充，即补偿电路1063进行5×10-8库伦的负电荷补偿。然后，检测电路1061可以继续检测脉冲电流产生电路200累计产生的电荷总量。如果判断电路1062判断脉冲电流产生电路200累计产生的电荷总量为6×10-8库伦的正电荷，则补偿电路1063可以继续进行3×10-8库伦的负电荷补偿。之后，检测电路1061可以继续检测脉冲电流产生电路200累计产生的电荷总量。当判断电路1062判断脉冲电流产生电路200累计产生的电荷总量超过安全电荷量时，补偿电路1063可以继续按照50％的比例进行电荷补偿，直至当判断电路1062判断脉冲电流产生电路200累计产生的电荷总量在安全电荷量以内时，补偿电路1063可以停止对脉冲电流产生电路200进行电荷补偿。当然，在补偿电路1063停止进行电荷补偿之后，检测电路1061可以继续检测脉冲电流产生电路200累计产生的电荷总量。也即是说，检测电路1061可以是一直处于工作状态，实时地进行检测，一旦检测出电荷量超过安全电荷量，补偿电路1063即可进行电荷补偿。
虽然以上结合附图和实施例对本发明进行了具体说明，但是可以理解，上述说明不以任何形式限制本发明。本领域技术人员在不偏离本发明的实质精神和范围的情况下可以根据需要对本发明进行变形和变化，这些变形和变化均落入本发明的范围内。

Claims (22)

  1. 一种用于神经刺激的脉冲电流产生电路，其特征在于，
    包括：
    模拟信号接收装置，其用于接收模拟信号；
    模数转换器，其将所述模拟信号转换为数字控制信号；
    电流信号控制器，其根据所述数字控制信号产生用于生成双向脉冲电流信号的脉冲电流参数；以及
    电流发生器，其根据所述脉冲电流参数生成用于神经刺激的所述双向脉冲电流信号，
    所述电流发生器能够根据所述脉冲电流参数生成不同精度的脉冲电流。
  2. 根据权利要求1所述的脉冲电流产生电路，其特征在于，
    在一个刺激周期内，所述双向脉冲电流信号的电荷总量在安全电荷量以内。
  3. 根据权利要求1或2所述的脉冲电流产生电路，其特征在于，
    所述脉冲电流参数包括负向脉冲宽度、负向脉冲幅度、正向脉冲宽度、正向脉冲幅度、以及脉冲间隔。
  4. 根据权利要求3所述的脉冲电流产生电路，其特征在于，
    所述电流发生器根据所述脉冲电流参数生成低精度脉冲电流或高精度脉冲电流，
    所述电流发生器在接收所述脉冲电流参数之后，判断所要生成的双向脉冲电流信号是否小于临界值，并且当所要生成的双向脉冲电流信号小于或等于临界值时，生成所述高精度脉冲电流；当所要生成的双向脉冲电流信号大于临界值时，生成所述低精度脉冲电流。
  5. 根据权利要求4所述的脉冲电流产生电路，其特征在于，
    当所述双向脉冲电流信号的所述负向脉冲宽度大于所述预设时长且所述负向脉冲幅度小于或等于所述临界值时，所述电流发生器生成 高精度脉冲电流。
  6. 根据权利要求4所述的脉冲电流产生电路，其特征在于，
    所述高精度脉冲电流的脉冲幅度的精度大于所述低精度脉冲电流的脉冲幅度的精度。
  7. 根据权利要求1所述的脉冲电流产生电路，其特征在于，
    所述双向脉冲电流信号的一个刺激周期内的正向脉冲电流或负向脉冲电流的电荷总量在安全电荷量以内。
  8. 根据权利要求1所述的脉冲电流产生电路，其特征在于，
    还包括电荷补偿电路，其根据所述双向脉冲电流信号的一个刺激周期内的电荷总量决定是否对所述电流发生器进行电荷补偿，以确保由所述电流发生器所生成的所述电荷总量在安全电荷量以内。
  9. 根据权利要求8所述的脉冲电流产生电路，其特征在于，
    所述电荷补偿电路包括：用于检测脉冲电流信号的检测电路、根据由所述检测电路所检测的脉冲电流信号来判断是否需要补偿的判断电路、以及基于所述判断电路的判断来产生补偿电荷的补偿电路。
  10. 一种电荷补偿电路，其特征在于，
    是用于对所述脉冲电流产生电路进行电荷补偿的电荷补偿电路，所述脉冲电流产生电路产生用于神经刺激的双向脉冲电流，
    所述电荷补偿电路包括：
    检测电路，其用于检测由所述脉冲电流产生电路生成的所述双向脉冲电流信号的一个刺激周期内的电荷总量；
    判断电路，其用于判断由所述检测电路检测的所述电荷总量是否超过安全电荷量；以及
    补偿电路，其用于当所述判断电路判断所述电荷总量超过安全电荷量时，产生具有净电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。
  11. 根据权利要求10所述的电荷补偿电路，其特征在于，
    在所述补偿电路中，当所述判断电路判断所述电荷总量为正值时，产生具有负值的补偿电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内，并且
    当所述判断电路判断所述电荷总量为负值时，产生具有正值的补偿电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。
  12. 根据权利要求10或11所述的电荷补偿电路，其特征在于，
    所述补偿脉冲电流信号的幅值低于预设幅值，并且所述补偿脉冲电流信号的周期小于所述双向脉冲电流信号的周期。
  13. 根据权利要求12所述的电荷补偿电路，其特征在于，
    所述预设幅值是能够对神经组织起到刺激作用的最小电流幅值。
  14. 根据权利要求10所述的电荷补偿电路，其特征在于，
    在所述双向脉冲电流信号中，正向脉冲电流信号的波形与负向脉冲电流信号的波形相反，
    所述检测电路检测所述正向脉冲电流信号的电荷量与所述负向脉冲电流信号的电荷量的绝对值，所述判断电路通过比较所述正向脉冲电流信号的电荷量与所述负向脉冲电流信号的电荷量的绝对值来判断所述电荷总量是否超过安全电荷量。
  15. 根据权利要求10所述的电荷补偿电路，其特征在于，
    所述检测电路检测由脉冲电流产生电路生成的所述双向脉冲电流信号的平均值，
    所述判断电路判断所述平均值的绝对值是否大于预设值，并且当所述平均值的绝对值大于所述预设值时，补偿电路产生具有净电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。
  16. 根据权利要求10所述的电荷补偿电路，其特征在于，
    所述检测电路检测由所述脉冲电流产生电路生成的双向脉冲电流信号的电流平均值，并将所述电流平均值转换为电压平均值，并且
    所述判断电路判断所述电压平均值的绝对值是否大于预设电压值，当所述电压平均值的绝对值大于所述预设电压值时，所述补偿电路产生具有净电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。
  17. 根据权利要求13所述的电荷补偿电路，其特征在于，
    当所述电压平均值的绝对值大于预设电压值，且所述电压平均值为正值时，所述补偿电路产生具有负值的净电荷量的补偿脉冲电流信号以使用于神经刺激的所述电荷总量在所述安全电荷量以内，并且
    当所述电压平均值的绝对值大于预设电压值，且所述电压平均值为负值时，所述补偿电路产生具有正值的净电荷量的补偿脉冲电流信号以使用于神经刺激的所述电荷总量在所述安全电荷量以内。
  18. 根据权利要求10所述的电荷补偿方法，其特征在于，
    所述补偿电路采用逐次逼近的电荷补偿方法。
  19. 一种电荷补偿方法，其特征在于，
    是用于对所述脉冲电流产生电路进行电荷补偿的电荷补偿方法，所述脉冲电流产生电路产生用于神经刺激的双向脉冲电流，
    所述电荷补偿方法包括：
    检测由所述脉冲电流产生电路生成的所述双向脉冲电流信号的一个刺激周期内的电荷总量；
    判断由所述检测电路检测的所述电荷总量超过安全电荷量；并且
    当判断所述电荷总量超过所述安全电荷量时，产生具有净电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。
  20. 根据权利要求19所述的电荷补偿方法，其特征在于，
    当判断所述电荷总量为正值时，产生具有负值的补偿电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内，并且
    当判断所述电荷总量为负值时，产生具有正值的补偿电荷量的补偿脉冲电流信号以使所述电荷总量在所述安全电荷量以内。
  21. 一种植入式视网膜电刺激器，其特征在于，
    包括：
    植入装置，其至少具有权利要求1至9中的任一项所述的脉冲电流产生电路；
    摄像装置，其用于捕获视频图像，并且将所述视频图像转换成视觉信号；
    视频处理装置，其与所述摄像装置连接，并且将所述视觉信号进行处理而生成调制信号；以及
    模拟信号发射装置，其将所述调制信号发送给所述植入装置，
    所述植入装置将所接收的所述调制信号转换成作为电刺激信号的所述双向脉冲电流信号，从而对视网膜的神经节细胞或双极细胞发放所述双向脉冲电流信号来产生光感。
  22. 一种植入式视网膜电刺激器，其特征在于，
    包括：
    植入装置，其至少具有权利要求10至18中的任一项所述的电荷补偿电路；
    摄像装置，其用于捕获视频图像，并且将所述视频图像转换成视觉信号；
    视频处理装置，其与所述摄像装置连接，并且将所述视觉信号进行处理而生成调制信号；以及
    模拟信号发射装置，其将所述调制信号发送给所述植入装置，
    所述植入装置将所接收的所述调制信号转换成作为电刺激信号的所述双向脉冲电流信号，从而对视网膜的神经节细胞或双极细胞发放所述双向脉冲电流信号来产生光感。
PCT/CN2017/104678 2016-09-30 2017-09-29 用于神经刺激的脉冲电流产生电路、电荷补偿电路和方法及植入式视网膜电刺激器 WO2018059568A1 (zh)

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