WO2018045482A1 - Système à ultrasons de régulation nerveuse - Google Patents

Système à ultrasons de régulation nerveuse Download PDF

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Publication number
WO2018045482A1
WO2018045482A1 PCT/CN2016/098158 CN2016098158W WO2018045482A1 WO 2018045482 A1 WO2018045482 A1 WO 2018045482A1 CN 2016098158 W CN2016098158 W CN 2016098158W WO 2018045482 A1 WO2018045482 A1 WO 2018045482A1
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transducer
nematode
signal
ultrasound
interdigital
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PCT/CN2016/098158
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English (en)
Chinese (zh)
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郑海荣
周伟
孟龙
王凯悦
牛丽丽
黄小伟
蔡飞燕
李飞
王辰
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深圳先进技术研究院
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Priority to PCT/CN2016/098158 priority Critical patent/WO2018045482A1/fr
Publication of WO2018045482A1 publication Critical patent/WO2018045482A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy

Definitions

  • the invention relates to the field of neuroscience and technology, in particular to a research device for ultrasonic neuromodulation, in particular to an ultrasound neuromodulation system.
  • neuromodulation treatment method is a popular treatment method in recent years, and has a good therapeutic effect on various neurological diseases, and the development speed is fast.
  • Neuromodulation exerts excitement, inhibition or regulation of neuronal or neuronal signal transduction in the central nervous system, peripheral nervous system, and autonomic nervous system adjacent or distant parts by implantable or non-implantable techniques, electrical or chemical means.
  • implantable or non-implantable techniques electrical or chemical means.
  • neuromodulation mainly uses electrical stimulation and drug means.
  • the most common neuromodulation techniques used in electrical stimulation include deep brain stimulation (DBS), spinal cord stimulation (SCS), and vagus nerve stimulation (VNS). These techniques are achieved by implanting electrodes into the brain, spinal cord, and vagus nerves of the human body, using electrical signals to stimulate the nerves for therapeutic purposes. The following is introduced one by one.
  • Deep brain electrical stimulation also known as brain pacemaker therapy
  • brain stereotactic surgery is used to implant electrodes in specific brain nuclei in the brain, and neurons can be inhibited by high-frequency electrical stimulation. Thereby playing a role in healing.
  • the deep stimulation of deep brain stimulation for Parkinson's disease is the globus pallidus and the thalamus intermediate nucleus (Vim).
  • the subthalamic nucleus (STN) electrical stimulation can also significantly relieve the tremor of Parkinson's disease patients. Muscle rigidity and bradykinesia symptoms.
  • Vagus nerve stimulation is a neuromodulation technique that entangles a spiral stimulating electrode in the left cerebral vagus nerve trunk and stimulates the vagus nerve through long-term and intermittent stimulation.
  • the principle may be related to the extensive projection of the vagus nerve, which can be projected through the solitary tract nucleus to the thalamus, amygdala and forebrain, and projected through the spinal cord network to the cerebral cortex. Therefore, vagus nerve stimulation can regulate the excitability of the cerebral cortex and thus control seizures.
  • a number of studies have shown that the efficacy of the vagus nerve in controlling seizures is significant over time and has a good effect on seizures in children.
  • the spinal cord electrical stimulation system places the stimulating electrode (strip electrode or needle-shaped puncture electrode) in the posterior part of the spinal epidural space, adjacent to the posterior column of the spinal cord, and then connected to the pulse generator implanted under the skin of the ankle. Stimulate the posterior column of the spinal cord and the sensory neurons in the posterior horn of the spinal cord for therapeutic purposes.
  • stimulating electrode strip electrode or needle-shaped puncture electrode
  • the drug neuromodulation technology is mainly used to treat cancer pain, Parkinson's disease, Alzheimer's disease (AD) by implanting a drug-loaded drug micro pump into brain tissue or spinal canal and slowly releasing the drug through a drug micro pump. ), refractory sputum, etc.
  • electrical stimulation of nerve regulation requires implanting electrodes in the human body to cause certain damage to the human body.
  • electrical stimulation technology stimulates a certain area of the brain without focusing.
  • Drug neuromodulation the implantation of the drug micropump will cause certain damage to the human body, and the method only uses long-term slow injection of drugs into the nerve tissue, thereby treating and alleviating neurological diseases, and has not been able to Neurological diseases are treated from the perspective of neuromodulation mechanisms.
  • Ultrasound neuromodulation is a new non-invasive brain stimulation and regulation technique in recent years. Based on the mechanical effects of ultrasound, the technique stimulates or inhibits the central nervous system of the stimulation site through different intensities, frequencies, pulse repetition frequencies, pulse widths, and durations. Effect, a reversible change in bidirectional regulation of neural function.
  • Fry et al. developed focused ultrasound that not only treats pain and Parkinson's disease, but also studies the structure and function of the brain circuit.
  • the University of Arizona team demonstrated for the first time through live animal experiments to achieve neuromodulation using low-frequency, low-pressure ultrasound. Therefore, it is very important to study the mechanism of ultrasound neuromodulation.
  • the present invention provides an ultrasonic neuromodulation system including a signal generator, a transducer, a microscope, a recording device, and a storage device, by storing a guest on a storage device,
  • the signal generator emits a sinusoidal electric signal, which generates a wave signal after passing through the transducer, exposes the object to the wave signal, and then uses the wave signal to stimulate the object.
  • the recording device records the behavior change of the object through the microscope, and the subsequent recordable
  • the information is quantified to achieve regulation of the nerves through the wave signal and to study the mechanism of the ultrasound nerve regulation, without the need to contact with the nerve, nor to implant the electrode and the drug injection pump.
  • It is an object of the present invention to provide an ultrasound neuromodulation system comprising a signal generator, a transducer, a microscope, a recording device and a reservoir, wherein the reservoir is for storing a guest,
  • the object is a nematode or a cell or a brain slice;
  • the signal generator is configured to output a sinusoidal electrical signal;
  • the transducer is configured to generate a wave signal according to the sinusoidal electrical signal;
  • the recording device is configured to pass The microscope records changes in the behavior of the object, the object being exposed to the wave signal.
  • the system further includes a power amplifier for power amplifying the sinusoidal electrical signal and transmitting the amplified sinusoidal electrical signal to the transducer.
  • the sinusoidal electrical signal has an amplitude greater than 150 millivolts and the amplified sinusoidal electrical signal has a power greater than 38 decibels.
  • the recording device is a high speed image sensor.
  • the transducer is a bulk wave transducer or an interdigital transducer, and when the transducer is a bulk wave transducer, the wave signal is a body wave signal; When the energy device is an interdigital transducer, the wave signal is an ultrasonic surface wave signal.
  • the interdigital transducer includes a piezoelectric substrate and a plurality of interdigital electrodes plated on the piezoelectric substrate.
  • the number of the interdigital electrodes is 1 or 2 or 4 or 8.
  • the piezoelectric substrate is 128°, YX double-sided polished lithium niobate or zinc oxide or aluminum nitride.
  • the reservoir is a polydimethylsiloxane PMDS channel, and the PMDS channel is bonded to a piezoelectric substrate of the interdigital transducer on.
  • the PMDS channel is tapered.
  • an M9 solution is placed in the PMDS lumen, and the nematode is placed in the M9 solution.
  • the reservoir is an agar plate, and the agar plate is placed on a piezoelectric substrate of the interdigital transducer.
  • the behavioral change when the object is a nematode, includes a number of return times of the nematode and a change in the frequency of the oscillation.
  • the reservoir is a slide placed on a piezoelectric substrate of the interdigital transducer.
  • the present invention has an advantageous effect of providing an ultrasonic neuromodulation system including a signal generator, a transducer, a microscope, a recording device, and a storage device.
  • the sine wave is emitted by the signal generator by storing a guest on the storage device.
  • the electrical signal generates a wave signal after passing through the transducer, exposing the object to the wave signal and then stimulating the object by using the wave signal, and finally recording the behavior change of the object by the recording device through the microscope, and then the quantitative analysis can be performed by the recorded information, thereby
  • the regulation of nerves by wave signals and the study of ultrasound neural regulation mechanisms do not require contact with the nerves, nor the need for implanted electrodes and drug injection pumps.
  • Embodiment 1 is a structural block diagram of Embodiment 1 of an ultrasound neural control system according to an embodiment of the present invention
  • Embodiment 2 is a structural block diagram of Embodiment 2 of an ultrasound neural control system according to an embodiment of the present invention
  • FIG. 3 is a structural block diagram of an interdigital transducer in an ultrasonic neuromodulation system according to an embodiment of the present invention
  • Embodiment 4 is a structural block diagram of Embodiment 1 of a storage device in an ultrasound neuromodulation system according to an embodiment of the present invention
  • FIG. 5 is a structural block diagram of Embodiment 2 of a storage device in an ultrasound neuromodulation system according to an embodiment of the present invention
  • 6a to 6e are schematic views showing a manufacturing process of the interdigital transducer
  • 6f to 6j are schematic views showing a process of fabricating a PDMS channel
  • Figure 6k is a schematic diagram showing the results of the combination of PDMS and interdigital transducer after plasma treatment
  • Figure 7 is a schematic view showing the experiment of C. elegans when PMDS is bonded to the interdigital transducer
  • Figure 8 shows the actual use of the ultrasound neuromodulation system
  • Figure 9a shows a schematic view of the morphology of nematodes in a normal state
  • Figure 9b to Figure 9d show three states of the nematode when the nematode is turned back;
  • Figure 10a shows a schematic of an ultrasound neuromodulation experiment on an agar plate
  • Figures 10b to 10e show schematic diagrams of nematode behavior without ultrasound
  • Figures 10f to 10i show a schematic diagram of the behavior of the nematode avoiding reaction after application of ultrasound
  • FIG. 11 is a structural block diagram of Embodiment 3 of a storage device in an ultrasound neuromodulation system according to an embodiment of the present invention.
  • Ultrasonic neuromodulation provides us with a non-invasive method of neuromodulation. It is necessary to accurately and effectively use ultrasound for neuromodulation, and to study the mechanism of ultrasound neuromodulation. important. Ultrasound neuromodulation lacks the scientific tools that can be applied to neuroscience and brain research. In addition, the physical and neurobiological mechanisms of ultrasound neuromodulation are still unclear.
  • Conventional ultrasound stimulation uses an ultrasound probe as an excitation source with a range of millimeters. It is used to study microscopic single-cell stimulation and specific specific neurons that stimulate the nematode. The traditional ultrasound system is difficult to integrate with the microscope. Dynamic responses to nerve cells, such as calcium imaging, cannot be observed in real time. In addition, conventional ultrasound systems cannot perform patch clamp recording of single cells.
  • the present invention provides an ultrasonic neuromodulation system which has good light transmittance and is compatible with a conventional microscope, and can quantitatively record calcium imaging of a nerve cell and a change of a single cell membrane potential in real time, and the chip generates
  • the sound field can be micron-sized, similar to the size of nerve cells, and can precisely stimulate a single cell and a certain neuron of a nematode.
  • This system is mainly used in the neuromodulation study of the neurological model C. elegans (C. elegans), and can also be applied to the neuroregulation of cells, brain slices, etc. researching.
  • Embodiment 1 is a structural block diagram of Embodiment 1 of an ultrasound neuromodulation system according to an embodiment of the present invention. As shown in FIG. 1, the system includes a signal generator 100, a storage device 200, a transducer 300, a microscope 400, and Recording device 500.
  • the storage unit 200 is configured to store a guest, and the object is a nematode or a cell or a brain slice.
  • the nematode can be a model organism such as Caenorhabditis elegans.
  • the signal generator 100 is configured to output a sinusoidal electrical signal.
  • the amplitude value of the sinusoidal electrical signal is greater than 150 millivolts in order to ensure the intensity of the stimulation signal.
  • the transducer 300 is configured to generate a wave signal according to the sinusoidal electrical signal.
  • the transducer is a bulk wave transducer or an interdigital transducer 301.
  • the wave signal is a body wave signal; when the transducer is an interdigital transducer, the wave signal is an ultrasonic surface wave signal.
  • Ultrasound probes used in hospital B-mode devices are one type of body wave transducers.
  • a bulk wave transducer consists of a housing, a matching layer, a piezoceramic disk transducer, a backing, an extraction cable, and a Cymbal array receiver.
  • the recording device 500 is configured to record a change in behavior of the object by the microscope 400, the object being exposed to the wave signal.
  • the recording device may be a high-speed image sensor CCD, and the movement of the nematode or the cell or the brain slice is recorded by the microscope, and the number of returning times of the nematode and the variation of the swing frequency may be analyzed through the recorded video and the like. Changes in cells, brain slices, or brain slices.
  • the present invention provides a neuromodulation system for a model organism (C. elegans), a nerve cell, a brain slice, including a signal generator, a transducer, a microscope, a recording device, and a storage device.
  • a guest object is stored on the storage device, and a signal generator generates a sinusoidal electric signal, and after the transducer generates a wave signal, the object is exposed to the wave signal, and the wave signal is used to stimulate the object, and finally the recording device passes through the microscope.
  • Embodiment 2 is a structural block diagram of Embodiment 2 of an ultrasound neuromodulation system according to an embodiment of the present invention. As shown in FIG. 2, the system further includes:
  • the power amplifier 600 is configured to perform power amplification on the sinusoidal electrical signal and transmit the amplified sinusoidal electrical signal to the transducer.
  • the power of the amplified sinusoidal electrical signal is greater than 38 decibels. This ensures a signal of sufficient strength to be transmitted to the surface acoustic wave microfluidic chip.
  • FIG. 3 is a structural block diagram of an interdigital transducer 301 in an ultrasonic neuromodulation system according to an embodiment of the present invention.
  • the interdigital transducer 301 includes a piezoelectric substrate 3011 and the pressure.
  • An interdigital electrode 3012 is plated on the electrical substrate.
  • the piezoelectric substrate In order to obtain a large electromechanical coupling coefficient, in a specific embodiment, 128° YX double-sided polished lithium niobate or zinc oxide or aluminum nitride is used as the piezoelectric substrate, and the number of the interdigital electrodes is 1 or 2 or 4 or 8.
  • Making an interdigital finger The process of the transducer mainly includes the processes of coating, lithography, coating, peeling and the like.
  • the fabrication process of the interdigital transducer in a specific embodiment is briefly described below, and the manufacturing process of the interdigital transducer is shown in FIGS. 6a to 6e.
  • Gluing On the surface of the completely cleaned piezoelectric substrate material, the positive photoresist AZ4620 was spin-coated at 5000 rpm for 30 s, and the chip was placed on a 120 ° C hot plate for baking for 3 min. We used a step meter to test the thickness of the photoresist. The thickness of the photoresist is about 5 ⁇ m, as shown in Figure 6a.
  • FIG. 7 is an experimental physical diagram of C. elegans when PMDS is bonded to an interdigital transducer. Referring to FIG. 7, it can be seen that in the specific use scenario, there are two interdigital electrodes 3012 distributed in the PMDS cavity. side.
  • Embodiment 1 of a storage device 200 in an ultrasound neuromodulation system is a structural block diagram of Embodiment 1 of a storage device 200 in an ultrasound neuromodulation system according to an embodiment of the present invention.
  • the storage device is a PMDS channel,
  • the PMDS channel is bonded to the piezoelectric substrate of the interdigital transducer.
  • the reservoir is a polydimethylsiloxane PMDS channel.
  • the PDMS channel can be fabricated in the following manner. Figures 6f to 6j show the fabrication process of the PDMS.
  • Pretreatment The residual impurities on the surface of the silicon substrate, such as dust and organic adsorbate, are removed by pickling, alcohol washing and water washing, and finally the silicon wafer is placed in a clean place to dry.
  • SU-8 (50) negative photoresist was spin-coated with a glue applicator, 3000 rpm, 30 s, SU-8 (50) thickness was about 50 ⁇ m. After the coating is completed, the silicon wafer is horizontally placed on a heating plate at 90 ° C for 1 h, and the solvent in the photoresist is volatilized to enhance the adhesion between the photoresist and the silicon wafer, and the pattern of FIG. 6f is obtained.
  • PDMS A glue and B glue are mixed according to mass ratio of 10:1, mixed evenly, poured into the petri dish where the silicon wafer is located, vacuum the culture dish to remove bubbles in PDMS, and finally The Petri dish was placed in an oven at 80 ° C for 30 min to cure the PDMS, as shown in Figure 6i.
  • Peeling PDMS The PDMS containing the pattern was cut with a scalpel and completely peeled off from the silicon wafer. Finally, the microcavity was perforated by a puncher to make an inlet and an outlet.
  • the prepared interdigital transducer and the PDMS channel are plasma-treated, the plasma processing power is 150W, the duration is 70s, and then the PDMS cavity end is glued down on the interdigital transducer for bonding, 80 Bake in a °C oven for 20 min.
  • a surface acoustic wave microfluidic chip for experimentation prepared as shown in Fig. 6k was obtained.
  • the PMDS lumen is tapered.
  • An M9 solution is placed in the PMDS channel, and the nematode is placed in the M9 solution.
  • FIG. 5 is a structural block diagram of Embodiment 2 of a storage device in an ultrasonic neuromodulation system according to an embodiment of the present invention.
  • the storage device may also be an agar plate. The agar plate is placed on the piezoelectric substrate of the interdigital transducer.
  • FIG. 11 is a structural block diagram of Embodiment 3 of a storage device in an ultrasound neuromodulation system according to an embodiment of the present invention.
  • the storage device is a slide.
  • the slide is placed on a piezoelectric substrate of the interdigital transducer.
  • the interdigitated transducer and the nematode are mainly taken as an example, and the present invention provides a neuromodulation system that can be used for model organisms (C. elegans), nerve cells, and brain slices, which can be quantified.
  • the angle of the neurological regulation of nematodes was analyzed.
  • the utility model comprises a signal generator, a transducer, a microscope, a recording device, a storage device and a power amplifier.
  • the sinusoidal electric signal is generated by the signal generator by storing the nematode on the storage device, and the wave signal is generated after the transducer is generated.
  • the object is exposed to the wave signal and then the wave signal is used to stimulate the object.
  • the recording device records the behavior change of the object through the microscope, and then the recorded information can be quantitatively analyzed, thereby realizing the regulation of the nerve through the wave signal and regulating the nerve.
  • the mechanism is studied without the need for contact with the nerves or the implantation of electrodes and drug injection pumps.
  • the PMDS cavity is bonded to the interdigital transducer to form a surface acoustic wave microfluidic chip.
  • Figure 7 is an experimental physical diagram of C. elegans when PMDS is bonded to an interdigital transducer. The PMDS is bonded to the interdigital transducer and connected to the wireworm container at one end of the PDMS cavity. The nematode suspended in the M9 solution, the other end of the channel is connected to the syringe through a thin tube, and the nematode is sucked into the PDMS channel by a pulling operation.
  • Figure Figure 8 shows the actual use of the ultrasound neuromodulation system. The fabricated experimental chip was placed under a stereo microscope, connected to a power amplifier and a signal generator, and the results of the experiment were recorded by a high-speed CCD. specific:
  • Figure 7 shows a schematic diagram of the experiment.
  • the PMDS is bonded to the interdigital transducer.
  • a container for carrying nematodes is attached at one end of the PDMS channel.
  • the inside of the container is filled with nematodes suspended in M9 solution, and the other end of the channel is fine.
  • the tubing is attached to the syringe, and the nematode is drawn into the PDMS lumen by a pulling operation, and then the excimer transducer excitation signal can be generated to generate ultrasonic waves to stimulate the nematode.
  • Figure 8 shows the entire experimental system.
  • the signal generator's signal sine wave electrical signal amplitude is greater than 150 mV, amplified by the power amplifier, sinusoidal
  • the power of the signal is greater than 38 dbm, and is transmitted to the surface acoustic wave chip as a signal of sufficient strength for the surface acoustic wave chip.
  • the time to control the nematode exposure to ultrasound (such as 0.5-1 minute) is the same as the time not exposed to ultrasound, compared with the number of times the nematode recurs and the variation of the nematode swing frequency in the same time, as shown in the figure.
  • 9a it is a nematode under normal conditions.
  • Figures 9b to 9d show the morphology of the nematode when it turns back.
  • the PMDS cavity is bonded to the interdigital transducer to form a surface acoustic wave microfluidic chip.
  • Figure 7 is an experimental physical diagram of C. elegans when PMDS is bonded to an interdigital transducer. The PMDS is bonded to the interdigital transducer and connected to the container of the wireworm at one end of the PDMS cavity. There is a nematode suspended in the M9 solution, and the other end of the channel is connected to the syringe through a thin tube, and the nematode is sucked into the PDMS channel by a pulling operation.
  • Figure 8 shows a diagram of the actual use of an ultrasound neuromodulation system. The fabricated experimental chip was placed under a stereo microscope, connected to a power amplifier and a signal generator, and the results of the experiment were recorded by a high-speed CCD. specific:
  • the structure of the PDMS channel is designed, and a copy of the channel is made using photolithography.
  • the PDMS channel is then formed by steps of pouring, curing, and punching.
  • a plasma treatment method is used to bond the channels to the already fabricated chips to fabricate the equipment used in the experiment.
  • the PDMS channel used in this embodiment is a tapered channel with a narrower width of the channel. The widest point can be 60 to 100 microns, and the narrowest can be 40 microns. When the nematode is inhaled into the lumen, it is fixed at the tip of the channel.
  • Figure 7 shows the experimental physical map.
  • the PMDS is bonded to the interdigital transducer.
  • a container carrying the nematode is connected.
  • the inside of the container is filled with nematodes suspended in the M9 solution, and the other end of the channel passes.
  • the thin tube is connected to the syringe, and the nematode is sucked into the PDMS channel by a pulling operation, and then the excitation signal of the interdigital transducer can be generated to generate ultrasonic waves to stimulate the nematode.
  • Neuronal calcium imaging The behavioral changes of nematodes were observed under a microscope. The nematodes were stimulated with ultrasound, and the calcium ion imaging of nematode neurons was observed in real time under a microscope to determine which neurons were activated. It is possible to determine which neurons are sensitive to ultrasound stimuli by the state in which the neurons are activated. In addition, stimulation of a single neuron can be achieved by using focused ultrasound, and the working state of the neuron is judged by observing neuronal calcium imaging.
  • the nematode depositor is an agar plate, and the agar plate is placed on the interdigital transducer to study changes in nematode behavior on the agar plate.
  • Figure 10a shows a schematic of an ultrasound neuromodulation experiment on an agar plate.
  • Figure 8 shows a diagram of the actual use of an ultrasound neuromodulation system. The fabricated experimental chip was placed under a stereo microscope, connected to a power amplifier and a signal generator, and the results of the experiment were recorded by a high-speed CCD. specific:
  • Agar plates can be prepared by prior art methods. After preparation, agar plates are placed on the interdigital transducers and the nematodes are picked onto agar plates for ultrasonic stimulation.
  • the above is a neuroregulatory system which can be used for model organisms (C. elegans), nerve cells and brain slices, and can analyze the neurological regulation of nematodes from a quantitative perspective.
  • the utility model comprises a signal generator, a transducer, a microscope, a recording device, a storage device and a power amplifier.
  • the sinusoidal electric signal is generated by the signal generator by storing the nematode on the storage device, and the wave signal is generated after the transducer is generated.
  • the object is exposed to the wave signal and then the wave signal is used to stimulate the object.
  • the recording device records the behavior change of the object through the microscope, and then the recorded information can be quantitatively analyzed, thereby realizing the regulation of the nerve through the wave signal and regulating the nerve.
  • the mechanism is studied without the need for contact with the nerves or the implantation of electrodes and drug injection pumps.
  • the invention uses the surface acoustic wave chip as a platform, combines the PDMS cavity and the neural model C. elegans, quantifies the results of ultrasonic neuromodulation, and completes the research on the mechanism of ultrasonic neuromodulation.
  • the key innovations of the present invention are:
  • Non-invasive, ultrasound neuromodulation is the regulation of nerves by ultrasound, no need to contact with nerves, nor need to implant electrodes and drug injection pumps, is a non-invasive neuromodulation.
  • the present invention combines a surface acoustic wave chip with a PDMS cavity and a microscope that can be quantized from the angle
  • a surface acoustic wave chip with a PDMS cavity and a microscope that can be quantized from the angle
  • neuronal knockout nematodes to achieve ultrasound neural regulation mechanisms that are accurate to a single nerve.
  • Combining surface acoustic wave chips with agar plates and microscopes allows for the study of nematode behavioral changes and is accurate to those neurons that play a leading role in nematode behavior.
  • the preparation process of the surface acoustic wave microfluidic chip is a standard MEMS process, and the device performance has good consistency, which lays a foundation for the repeatability of the experiment.
  • the nematodes of the same medium in the process of nematode culture are uniformly cultured from the fertilized egg period. At the same time, the nematodes are in the same growth period, and multiple nematodes can be continuously tested.
  • the point of protection of the present invention is to study the mechanism of ultrasound neuromodulation using a surface acoustic wave chip.
  • surface acoustic wave chip realizes the research on the mechanism of ultrasonic neuromodulation from the microscopic point of view by combining surface acoustic wave chip and PDMS cavity.
  • the existing methods all need to implant corresponding devices in the human body, which cause certain damage to the human body, and they all regulate a large number of nerve nuclei in the human body without focusing on a single nerve. Yuan, explores neuromodulation from the perspective of neurons.
  • the ultrasonic neuromodulation used in the present invention does not require implantation of any device in the human body, and is a non-invasive regulation method.
  • microfluidic chips have been rapidly developed, and the combination of microfluidic chips and surface acoustic wave devices has received extensive attention. Combined with surface acoustic wave chips and PDMS channels, ultrasound can be used to study the mechanism of ultrasound neuromodulation from the perspective of microscopic neurons.
  • the present invention can be applied to studies of neuromodulation mechanisms such as cells and brain slices in addition to application in neuromodulation studies of Caenorhabditis elegans.
  • the cavity of the PDMS can be flexibly designed.
  • a circular channel can be used to make the nematode move flexibly in the circular cavity.
  • the tapered channel can be used to fix the nematode, and other shapes can be used.
  • the lumen thus functions to accommodate nematodes or fixed nematodes.
  • the surface acoustic wave chip-interdigital transducer can be flexibly designed in size and shape.
  • lithium niobate single crystal is used as the piezoelectric substrate.
  • Thin film piezoelectric materials such as zinc oxide and aluminum nitride.
  • a bulk wave transducer prepared based on a piezoelectric thin film material such as zinc oxide or aluminum nitride can also be used.
  • the storage medium may be a magnetic disk, an optical disk, a read-only memory (ROM), or a random access memory (RAM).

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Abstract

L'invention concerne un système à ultrasons de régulation nerveuse comprenant un générateur de signal (100), un transducteur (300), un microscope (400), un dispositif d'enregistrement (500) et un dispositif de stockage (200). Le dispositif de stockage (200) est utilisé pour stocker un objet, l'objet étant un nématode ou une cellule ou une tranche cérébrale. Le générateur de signal (100) est utilisé pour émettre un signal électrique d'onde sinusoïdale. Le transducteur (300) est utilisé pour générer un signal d'onde selon le signal électrique d'onde sinusoïdale. Le dispositif d'enregistrement (500) est utilisé pour enregistrer un changement de comportement de l'objet au moyen du microscope (400), l'objet étant soumis au signal d'onde. Un nerf est régulé au moyen d'ultrasons ; le système ne doit pas être en contact avec le nerf et une électrode et une pompe d'injection de médicament ne doivent pas être implantées ; le système à ultrasons de régulation nerveuse est un moyen non invasif de régulation nerveuse.
PCT/CN2016/098158 2016-09-06 2016-09-06 Système à ultrasons de régulation nerveuse WO2018045482A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115136899A (zh) * 2022-05-24 2022-10-04 温州医科大学 一种用于生物实验的ivc笼具

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