Electrical stimulation systems with deformable stimulator and related methods

Abstract

This invention provides a wireless powered electrical stimulation system. In one embodiment, said system comprises: a) a power transmitter, said power transmitter comprises a wearable transmitter coil and a portable control circuit for wireless power transfer; and b) a wireless electrical stimulator said wireless electrical stimulator comprises a power management module and a pulse stimulation module configured to apply electrical stimulations on target tissue. In one embodiment, said wireless electrical stimulator further comprise a sensing module configured to monitor the motility or electrophysiological signals of target tissue. In one embodiment, said wireless electrical stimulator is made of soft or flexible materials. Said wireless electrical stimulator is configured to deliver through natural orifice without open surgery. Related minimally invasive implantation method is also provided.

Description

ELECTRICAL STIMULATION SYSTEMS WITH DEFORMABLE STIMULATOR AND RELATED METHODSFIELD OF THE INVENTION

[0001] The present invention generally relates to wireless powered medical devices for the minimally invasive electrical stimulation therapy to restore the normal functions of typical muscle groups, like gastrointestinal tract.BACKGROUND OF THE INVENTION

[0002] Functional electrical stimulation (FES), a method using electrical stimulation to restore the degenerated function of typical muscle groups, has been wildly used in clinical. For example, it helps patients with spinal cord injury regaining some normal functions, like grasping and walking. Various systems, sensors, and algorithms are investigated to improve the performance. Although transdermal electrical stimulation is a non-invasive method, it needs high voltages or currents to apply effective stimulation across the skin. Compared with it, implantable stimulators directly apply electrical pulses to control the target muscle group. However, the operation time of the device is limited by the battery capacity. Frequent replace batteries would increases the risk of infection and other side effects.

[0003] Wireless power transfer is a promising solution for the implantable medical devices. However, efficient power transfer through deep tissue still remains challenging because tissues greatly attenuate the electromagnetic energy. Moreover, the efficiency of wireless power transfer highly depends on the orientation, position, and the geometry configuration of the receiver coils.

[0004] Here, the system, device, and related implantation procedures of the wireless electrical stimulation are provided. The electrical stimulator is powered by the wireless power transfer system, which prolongs the lifetime, eliminates the need of replace batteries and related potential risks. Endoscopy delivery procedures through natural orifice are also disclosed for the minimally invasive delivery procedure. It avoids the open surgery for the implantation and thus reduces the risk of infection during recovery.SUMMARY OF THE INVENTION

[0005] Systems, devices, materials, and related methods are disclosed for the wireless electrical stimulation systems. The system consists of a transmitter coil for the wireless power transfer and an electrical stimulator with receiver coils. The transmitter coils are placed outsidethe body and generate alternative magnetic fields for the wireless power transfer in deep tissue. The electrical stimulator composes of receiver coils, a power management module, a pulse generator, and a pair of electrodes. Moreover, related minimally invasive delivery methods are also provided. The electrical stimulator is delivered or implanted through natural orifices by the endoscopy without the need of open surgery.

[0006] In one aspect, the wireless power transfer systems are provided. In general, the system includes one or more transmitter coils with matched capacitors, a power supply and related control circuits. Alternative current is applied on the transmitter coils. Based on Faraday’s law, the transmitter coils generate alternative magnetic fields. In addition, the transmitter coils are configured with different geometry shapes. In some embodiments, the transmitter coil has a solenoid shape, which generates strong magnetic fields within the region enclosed by the coils. In some embodiments, the coils are a pair of Helmholtz coils. In some embodiments, the coils are braided into a pair of solenoids coils. In some embodiments, the coils are braided into a planar pad.

[0007] In some embodiments, direct current (DC) power supply is converted into alternative current (AC) by a full-bridge inverter. The frequency is controlled by the pulse width modulate signal generated by the control circuits.

[0008] In some embodiments, a signal generator generates alternative voltage and corresponding signal is amplified by a power amplifier.

[0009] In one aspect, the wireless electrical stimulator is provided. The receiver coils compass a closed area. While alternative magnetic fields transmit through the closed loop, an alternative voltage is induced in the receiver coils. Then the alternative voltage is converted to the direct voltage by a full-bridge rectifier. And the voltage with high amplitudes and noises are regulated to a stable voltage by the power management module. Finally, the pulse generator generates pulse voltages with typical frequency, amplitude, and pulse width.

[0010] In some embodiments, the electrical stimulator may also include a micro-controller unit (MCU) to set these parameters.

[0011] In some embodiments, a constant current module follows the pulse generator. It coverts the pulse voltage into pulse currents with constant amplitude while applied to various loads.

[0012] In some embodiments, the electrodes are fabricated in the form of microneedles that penetrates through the tissues.

[0013] In some embodiments, the power management module includes a full-bridge rectifier and a linear low dropout regulator (LDO).

[0014] In some embodiments, the power management module may also contain a buck converter for more efficient power transfer.

[0015] In one aspect, endoscopy delivery methods and related applications are provided. Natural orifices, like gastrointestinal tract, urinary tract, and etc, are accessible by endoscopies, which provides a minimally invasive method for the implantation or delivery of the electrical stimulator.

[0016] In some embodiments, peroral endoscopic myotomy (POEM) procedure is conducted to create a tunnel between the mucosal layer and the muscle layer of the esophagus. Then, the miniaturized electrical stimulator is delivered into the esophagus and implanted through the tunnel. After that, the tunnel is sutured or closed by several endo clips.

[0017] In some embodiments, the electrical stimulator is integrated on a medical device, like a stent. They are delivered through the natural orifice by a thin catheter. The electrical stimulator retains inside body after releasing the stent.

[0018] In some embodiments, the electrical stimulator is used in gastrointestinal tract to regulate GI disorders, like irritable bowel diseases, gastroesophageal reflux disease, or faecal incontinence.

[0019] In some embodiments, the electrical stimulator is used in the bladder or urinary tract to manage the urinary incontinence.

[0020] In some embodiments, the electrical stimulator is used in vagina for the treatment of dysfunction of the pelvic floor muscles.BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Non-limiting embodiments of the present invention will be described by means of an example combined with figures, which are schematic and are not intended to be drawn to scale. In the figures, each identical or nearly identical component illustrated is typically represented by a single number. For purposes of clarity, not every component is labelled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention. In the figures:

[0022] FIG.1A illustrates the minimally invasive implantation method of a wireless electrical stimulator and its system, including a wireless power transmitter and a wireless electrical stimulator. The wireless power transmitter includes a wearable power transmitter and a portable control board.

[0023] FIG. IB shows a photograph of a typical prototype of the wireless electrical stimulation system on a human phantom.

[0024] FIG. 2A shows the 3D magnetic field generated by the power transmitter.

[0025] FIG. 2B shows the uniform magnetic field distribution within the power transmitter along the axial direction (X axis) and radial direction (Y axis) of the transmitter coil

[0026] FIG. 3 shows the block diagram of the portable control box, which includes a rechargeable battery, a power management circuit, a control circuit, and matching capacitors.

[0027] FIG. 4 illustrates the block diagram of an alternative design of the portable control box, including a signal generator, a power amplifier, and an antenna auto tuner.

[0028] FIG. 5 shows the block diagram of the wireless electrical stimulator, which includes a receiver coil, a power management module, and a pulse stimulation module with one or more pairs of electrodes.

[0029] FIG. 6A shows adjustable constant current stimulations with different load resistances.

[0030] FIG. 6B shows biphasic constant current pulse stimulations with different load resistances.

[0031] FIG. 7 shows pulse stimulations with programmable frequencies and pulse width in this invention. FIG. 7A shows a typical frequency of 10 Hz for the pulse stimulations.

[0032] FIG. 7B shows a typical frequency of 20 Hz for the pulse stimulations.

[0033] FIG.7C shows a typical frequency of 50 Hz for the pulse stimulations.

[0034] FIG. 7D shows typical pulse widths ranging from 100 microseconds to 500 microseconds for the pulse stimulations.

[0035] FIG. 8A illustrates a typical design of the wireless electrical stimulator including a stent, an elastic coil, and a stretchable pulse generator with one or more pairs of electrodes.

[0036] FIG. 8B shows a photograph of a prototype of the elastic coil as a receiver coil.

[0037] FIG. 8Cshows photographs of a stretchable pulse generator with various deformations, including twisting, bending, and stretching.

[0038] FIG. 8D shows a photograph of an integrated wireless electrical stimulator with stretching.

[0039] FIG. 9 shows X-ray images of a non-invasive transoral delivery procedure of the wireless electrical stimulator.

[0040] FIG. 10A illustrates components of a delivery tool includes a balloon catheter, a block ring, a soft tip, a flexible shell and a handle.

[0041] FIG. 10B illustrates the wireless electrical stimulator assembled within the delivery tool.

[0042] FIG. 11 illustrates an alternative design of the wireless electrical stimulator in a miniature and flexible form. FIG. 11 A shows the top view of the wireless electrical stimulatorincluding a flexible substrate, printed receiver coils, electronic components, a printed antenna, a battery and a pressure sensing module.

[0043] FIG. 11B shows the bottom view of the wireless electrical stimulator including the substrate, printed receiver coils, one or more pairs of electrical stimulations electrodes, and one or more sensing electrodes.

[0044] FIG. 12A, B shows a typical design of the delivery tool including a soft tip assembled with a transparent holder. FIG. 12C illustrates the assemble process of the delivery tool with an endoscope.

[0045] FIG. 13 shows a minimally invasive transoral delivery procedure of the wireless electrical stimulator through a submucosal tunnel created by an endoscope.DETAILED DESCRIPTION OF THE INVENTION

[0046] This invention provides a system for stimulating a target tissue with electrical signals. In one embodiment, said system comprises: a) A wireless power transfer module configured to operate at a resonant frequency, comprising one or more wearable transmitter coils and a portable control circuit; and b) A wireless and deformable electrical stimulator configured for placement into a subject and operating at said resonant frequency, comprising at least one receiver coil, a power management module and a stimulation module; wherein said wireless power transfer module generates an alternative magnetic field which is passed through said at least one receiver coil to induce an alternative voltage which is converted to a stable voltage by said power management module to power said stimulation module to generate said electrical signals.

[0047] In one embodiment, said portable control circuit comprises: a) a rechargeable battery, a power management circuit providing constant currents and different voltages, a pulse width modulation generator, a full-bridge inverter, metal-oxide-semiconductor field-effect transistor (MOSFET) drivers; and one or more matching capacitors; or b) a rechargeable battery, a power management circuit, a signal generator, a power amplifier, and an antenna auto tuner configuring said one or more wearable transmitter coils operating at said resonant frequency.

[0048] In one embodiment, said resonant frequency ranges from 100k Hz to 1G Hz.

[0049] In one embodiment, said electrical signals comprise a) monophasic or biphasic voltage pulse or pulse train; or b) monophasic or biphasic current pulse or pulse train; or c) charge balanced current pulse or pulse train.

[0050] In one embodiment, said electrical signals comprises one or more set of parameters selected from the group consisting of: a) a current amplitude ranging from 3 mA to 15 mA; b)a frequency ranging from 1 Hz to 1000 Hz; and c) a pulse width ranging from 100 microseconds to 200 milliseconds.

[0051] In one embodiment, said stimulation module comprises one or more electrodes for delivering said electrical signals into said target tissue.

[0052] In one embodiment, said one or more electrodes comprises one or more characteristics selected from the group consisting of a) said one or more electrodes are needle-shaped; b) each of said one or more electrodes are separated by 0.1 mm to 30 mm; and c) said one or more electrodes has a length ranging from 50 um to 300 um.

[0053] In one embodiment, said power management module comprises a rectifier circuit for converting said alternative voltage to said stable voltage, wherein said rectifier circuit is selected from the group consisting of: a) a plurality of diodes and capacitors; b) a full-bridge rectifier; c) a linear low dropout regulator; d) a boost converter to increase said stable voltage; and e) a buck converter to decrease said stable voltage.

[0054] In one embodiment, said wireless and deformable electrical stimulator is adapted for placement into said subject via a natural orifice selected from the group consisting of gastrointestinal tract, trachea, urinary tract, and vagina.

[0055] In one embodiment, said wireless and deformable electrical stimulator further comprises a microcontroller configured to perform one or more functions selected from the group consisting of: a) set parameters of said electrical signals; b) control said stimulation module; and c) process data for wireless communication via radio frequency protocols.

[0056] In one embodiment, said wireless and deformable electrical simulator further comprises a sensing module configured to monitor movement or pressure inside said subject.

[0057] In one embodiment, said wireless and deformable electrical stimulator further comprises one or more sensing electrodes configured to measure electrophysiological signals of said target tissue.

[0058] In one embodiment, said one or more wearable transmitter coils are selected from the group consisting of a single solenoid, a planar coil, a pair of Helmholtz coils, a pair of solenoid coils braided by a single wire, and a planar coil with an additional resonator coil configured to operate at same resonant frequency.

[0059] In one embodiment, said wireless and deformable electrical stimulator further comprises a mechanical skeleton; said at least one receiver coil is an elastic coil braided along said mechanical skeleton.

[0060] In one embodiment, said wireless and deformable electrical stimulator is made of materials allowing said electrical stimulator to be stretchable up to 50%.

[0061] In one embodiment, said materials comprise dielectric materials for substrates and encapsulation; and intrinsic conductive materials for circuit traces and contact pads; wherein a) said dielectric materials are selected from the group consisting of polydimethylsiloxane (PDMS), polyurethane (PU), styrene ethylene butylene styrene (SEBS), polyimide (PI), polyethylene terephthalate (PET) and hydrogels; b) Said intrinsic conductive materials are selected from the group consisting of silver nanowires, carbon nanotubes, gold nanowires, poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), printed copper wire and gallium-based liquid metal.

[0062] This invention also provides a method for delivery of the system of this invention to said target tissue. In one embodiment, said method comprises the steps of: a) Inserting a delivery tool through an opening to a desired location, said delivery tool comprises a balloon and a stent compressed within said delivery tool; said stent is integrated with said wireless and deformable electrical stimulator; b) Releasing said stent integrated with said wireless electrical stimulator; and c) Inflating said balloon so that said stimulation module contacts said target tissue.

[0063] In one embodiment, said opening is a natural orifice selected from the group consisting of gastrointestinal tract, trachea, urinary tract, and vagina.

[0064] In one embodiment, said delivery tool further comprises a flexible shell, a soft tip, a block ring, and a balloon with a flexible catheter.

[0065] In one embodiment, said method comprises the steps of: a) Creating a submucosal tunnel between a mucosal layer and a muscle layer by a standard endoscope; b) Assembling said wireless and deformable electrical stimulator with a delivery tool connected with said standard endoscope; c) Inserting said wireless and deformable electrical stimulator into said submucosal tunnel; d) Configuring said wireless and deformable electrical stimulator to deliver electrical signals to said target tissue; and e) Closing said submucosal tunnel.

[0066] In one embodiment, said delivery tool comprises a soft tip, and a transparent holder configured to connect said wireless electrical stimulator and a standard endoscope.

[0067] In one embodiment, said target tissue is a muscle layer in the gastrointestinal tract, urinary tract, or reproduction system.

[0068] This invention provides a wireless powered electrical stimulation system. In one embodiment, said system comprise: a) a wearable transmitter, said wearable transmitter comprises a transmitter coil and a control board for the wireless power transfer; and b) a wireless electrical stimulator, said wireless electrical stimulator comprises a powermanagement module and a pulse stimulation module. It may also include a sensing module for the closed-loop electrical stimulation.

[0069] In one embodiment, the control board comprises: a) a rechargeable battery; b) a power management circuit providing constant currents and different voltages; c) a control circuit comprising a pulse width modulation generator; d) a full-bridge inverter; e) metal-oxide- semiconductor field-effect transistor (MOSFET) drivers, and f) one or more matching capacitors.

[0070] In one embodiment, an alternative design of the control board comprises: a) rechargeable battery; b) a power management module; c) a signal generator that generates alternative signals; d) a power amplifier, and e) an antenna auto tuner matching the transmitter coil to the resonant frequency.

[0071] In one embodiment, said transmitter coil has a geometry configuration that is planar, pairs of Helmholtz, single solenoid, or pairs of solenoids with a diameter ranging from 5cm to 80cm. In some embodiment, said transmitter coil comprises a planar transmitter coil and a separate planar resonant coil. Both coils operate at the same resonant frequency. Said resonant coil boost power by amplify generated magnetic field intensity.

[0072] In one embodiment, said wearable transmitter generates magnetic field at a frequency ranging from 100K Hz to 100M Hz.

[0073] In one embodiment, the wireless electrical stimulator further comprises a receiver coil, one or more pairs of electrodes, or a micro controller for parameter settings and wireless communication.

[0074] In one embodiment, said power management module includes a rectifier circuit that converts the alternative current into direct current and a voltage regulator that provides stable voltage.

[0075] In one embodiment, said pulse generator module comprises a pulse generator for generating current or voltage pulse signals with programmable amplitude, frequency, and pulse width.

[0076] In one embodiment, said pulse generator generates current or voltage pulse signals at a frequency ranging from 1Hz to IK Hz.

[0077] In one embodiment, said pulse generator generates current at an amplitude ranging from 3 mA to 15 mA.

[0078] In one embodiment, said pulse generator generates current or voltage pulse signals at a pulse width ranging from 100 microseconds to 200 milliseconds.

[0079] In one embodiment, said pulse generator generates charge balanced current pulse signals to avoid tissue damage and electrodes corrosion.

[0080] In one embodiment, the receiver coil comprises a ferrite core to increase to wireless power transfer efficiency.

[0081] In one embodiment, each of said one or more pairs of electrodes is a needle shaped electrode for applying electrical stimulation through tissue.

[0082] In one embodiment, said one or more pairs of electrodes are separated by 0.1 mm to 30 mm.

[0083] In one embodiment, said one or more pairs of electrodes has a length ranging from 50 um to 300 um.

[0084] In one embodiment, said one or more pairs of electrodes has a shape selected from the group consisting of cones, prisms, or pricks.

[0085] In one embodiment, the wireless electrical stimulator comprises substrate or encapsulation made of one or more dielectric material selected from the group consisting of polydimethylsiloxane (PDMS), styrene ethylene butylene styrene (SEBS), polyurethane (PU), poly imide (PI), and hydrogels.

[0086] In one embodiment, the wireless electrical stimulator comprises circuit traces and contact pads made of one or more intrinsic conductive materials selected from the group consisting of silver nanowires, carbon nanotubes, gold nanowires, poly(3,4- ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), or liquid metal.

[0087] This invention provides a method for endoscopy delivery of the wireless powered electrical stimulation system of this invention for minimally invasive electrical stimulation therapy inside natural orifices, said wireless powered electrical stimulation system further comprises one or more pairs of electrodes. In one embodiment, said method comprises the steps of: a) Inserting a delivery tool through a natural orifice, said delivery tool comprises a balloon and a stent compressed within said delivery tool; said stent is integrated with said wireless electrical stimulator: b) Releasing said stent integrated with said wireless electrical stimulator; c) Inserting one or more pairs of electrodes into muscle tissue by inflating the balloon.

[0088] In one embodiment, said natural orifices comprises gastrointestinal tract, trachea, urinary tract, or vaginal.

[0089] In one embodiment, the delivery tool comprises a flexible shell, a soft tip for safe interaction with tissue, a block ring, a balloon catheter for electrodes insertion through tissue, and a handle.

[0090] In one embodiment, for another endoscopy delivery method of this invention, the delivery procedure comprises the following steps: i) Slicing open a gastrointestinal mucosal by an endoscopy to create a submucosal tunnel between said gastrointestinal mucosal layer and a gastrointestinal muscle layer; and ii) Implanting said wireless stimulator into said tunnel; iii) Closing said tunnel by several endoscopic clips.

[0091] The invention will be better understood by reference to the experimental Details which follow, but those skilled in the art will readily appreciate that the specific experiments described are only for illustrative purposes and are not meant to limit the inventions as described herein, which is defined by the claims that follow thereafter.

[0092] The present invention provides a wireless electrical stimulation system for long-term in vivo electrical stimulation therapy. Referring to FIG. 1A, this invention includes two parts, a wearable transmitter 110 with a portable control board 120 for wireless power transfer and a wireless electrical stimulator 100 that applies pulse signals. Alternative current flows through the transmitter coils 110 that generate alternative magnetic fields. However, the intensity of the magnetic fields decays quickly as the distance increases. Moreover, tissues also attenuate electromagnetic energy. Therefore, a transmitter coil 110 with a reasonable design is important for wireless power transfer in deep tissues. The geometry configuration of the transmitter coil 110 greatly affects the wireless power transfer.EXAMPLE 1

[0093] In some embodiments, the transmitter coil 110 is a single solenoid that generates a strong magnetic field near the central region within the coil. Movement or orientation of the receiver may induce higher voltage accidently, which leads to safety issues. In some embodiments, the transmitter coil 110 is a pair of Helmholtz coils, which generates uniform magnetic fields within the region of the coil. However, the magnetic intensity is weaker than the single solenoid coil. In some embodiments, the transmitter coil 110 is a pair of solenoids coil braided by a single wire. It generates a uniform and relatively strong magnetic field within the coil. In some embodiments, the transmitter coil 110 has a diameter ranging from 30 cm to 80 cm that could accommodate various body shapes of different individuals. In some embodiments, the wearable transmitter coil 110 is fabricated in the form of overalls. Referring to FIG. IB, the photo shows a typical design of the transmitter coil 110 on a human phantom. Referring to FIG.2a & 2b, the wearable transmitter coil 110 generates a uniform magnetic field within the transmitter coil 110 to power implants in deep tissue.

[0094] The implantable medical devices 100 are placed within the region of the transmitter coil 110. Based on Faraday’s law, the receiver coil 102 in the electrical stimulator 100 inducesan alternative voltage with the same frequency as the magnetic fields. Moreover, the amplitudes of the induced voltage are associated with the intensity of the magnetic fields and the loop area enclosed by the receiver coils 102. In some embodiments, the receiver coils 102 have a ferrite core, which increases the magnetic permeability and hence increases the received voltage. In some embodiments, the receiver coils 102 are configured with three orientations and connected in parallel to compensate for the efficiency loss due to the angular mismatch.EXAMPLE 2

[0095] The transmitter coil 110 is driven by alternative currents with typical frequency, which mainly depends on the geometry configurations of the transmitter coils. Referring to FIG. 3, the portable control board 120 includes a rechargeable battery, a power management module 121, a control circuit 122, and adjustable matching capacitors 123. The control circuit 122 includes a pulse width modulation (PWM) generator providing square wave signals with adjustable frequencies ranging from 100 kHz to IM Hz, a full bridge inverter that converts direct current into alternative currents and then drives the transmitter coil, a metal-oxide- semiconductor field-effect transistor (MOSFET) driver that powers the full bridge inverter.

[0096] In some embodiments, the transmitter coil 110 has a planar form with resonant frequency ranging from 1 MHz to 1 GHz. Referring to FIG.4, a signal generator directly generates an alternative voltage with the resonant frequency of the power transmitter coil. Then the control signal is amplified by a power amplifier before it is applied to the transmitter coil. In some embodiments, an antenna auto tuner connects the output of the power amplifier with the transmitter coil 110. It automatically adjusts on board capacitors and inductors to match the transmitter coil 110 to the resonant frequency.

[0097] In some embodiments, a sperate planar resonant coil is provided. It is configured in parallel to said transmitter coil 110 to amplify the magnetic field intensity. Said resonant coil is also configured to operate at the same resonant frequency of said transmitter coil 110.EXAMPLE 3

[0098] Referring to FIG. 5, the wireless electrical stimulator 100 contains a receiver coil 102, a power management module 103-1, a pulse stimulation module 103-2, and one or more pairs of electrodes. As mentioned before, the receiver coil induces alternative voltage within the time-variant magnetic fields, which is not suitable to power the following circuits. Therefore, the alternative voltage is converted into direct voltage by a rectifier circuit. In some embodiments, the rectifier circuit consists of a diode that blocks half of the alternative wave and thus leads to poor power efficiency. In some embodiments, the rectifier circuit is a fullbridge rectifier, which is more efficient than a single diode. The converted voltage is smoothedby a capacitor. Furthermore, the voltage is regulated to a stable voltage by a linear low dropout regulator (LDO). In some embodiments, a boost converter boosts the voltage to a higher level to drive the constant current source. In some embodiments, the pulse stimulation module contains a micro-controller unit (MCU) for wireless communication and pulse parameters setting. A constant current module that converts voltage pulses into constant current pulses with different loads.

[0099] According to previous research, amplitudes, frequency, and pulse width, all affect the performance of the electrical stimulation therapy. In general, a pulse train consists of a series of pulse signals with constant intervals and pulse width. In some embodiments, the pulses are monophasic signals. However, the accumulated charge may lead to muscle fatigue. In some embodiments, the stimulation signals are biphasic pulses as shown in FIG. 6a, which results in balanced charging to the tissue. In some embodiments, the stimulation signals are voltage pulses. It applies pulses with constant voltage amplitudes to the tissue. Due to the parasitic capacitance between tissue-electrode, the charging current varies during stimulation. Overcharging has related safety issues. In some embodiments, the stimulation signals are current pulses, typically ranging from 3 mA to 8 mA as shown in FIG. 6b. Previous study shows that low-frequency electrical stimulation induces effective muscle movement. Specifically, the frequency ranges from 1 Hz to 1000 Hz. In some embodiments, both frequency and pulse width can be adjusted by MCU as shown in FIG. 7a, 7b, 7c and 7d.

[0100] In some embodiments, the wireless electrical stimulator contains a rechargeable battery that can be wirelessly recharged. It has a capacity ranging from ImAh to 2000 mAh to power the whole circuit for a typical period, ranging from 5 minutes to 60 minitues.EXAMPLE 4

[0101] Referring to FIG. 8A, in some embodiments, a typical wireless electrical stimulator 100 includes a stent as a mechanical skeleton 101, an elastic coil as the receiver coil 102, and a stretchable pulse generator 103 with one or more pairs of electrodes. In FIG. 8B the elastic coil is fabricated by infusing liquid metal into a single silicone tube. Then the elastic coil is braided along the skeleton of the stent. The stretchable pulse generator is fabricated with soft and flexible materials. In some embodiments, dielectric materials, like polydimethylsiloxane (PDMS), polyurethane (PU), styrene ethylene butylene styrene (SEBS), and hydrogels, are used as the substrates and encapsulation. Intrinsic conductive materials are to form circuit traces and contact pads. In some embodiments, the intrinsic conductive materials include but not limited to silver nanowires, carbon nanotubes, gold nanowires, poly(3,4- ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), or liquid metal. In someembodiments, the electrical stimulator is coated with a layer of parylene or a layer of antibacterial hydrogel. Referring to FIG. 8C, a typical prototype of the stretchable circuit undergoes various deformations, like twisting, bending, and stretching. Referring to FIG. 8D, intrinsic materials and transformable structures jointly enable the integrated wireless electrical stimulator to undergo 50% stretching.EXAMPLE 5

[0102] Referring to FIG. 9, the non-invasive endoscopy delivery through the natural orifice is provided. In some embodiments, the wireless electrical stimulator 100 is integrated on a stent. Firstly, the stent with the electrical stimulator is compressed within the delivery catheter 130. Then, the catheter is delivered through the natural orifice. After releasing the stent, the selfexpandable stent structure helps the device retain inside the narrow channel. Finally, a balloon catheter 132 is inflated to fully release the wireless electrical stimulator and provide electrodes tight contact with tissues. In some embodiments, the electrodes are made in the form of microneedles, which are then inserted across the mucosal layer and the needle tips contact with the muscle layer. In some embodiments, the electrodes are mounted on the out layer of the stent. They directly contact with the tissue since the stent applies normal force to the tissue.

[0103] In some embodiments, the electrodes are directly in contact with the target muscle group. In some embodiments, the electrodes are fabricated in the form of microneedles that penetrates the tissue for effective electrical stimulation. The length of the microneedle ranges from 300um to 800um. The diameter of the microneedle ranges from 100 um to 600 um.

[0104] Referring FIG. 10A, the delivery catheter 130 for the non-invasive endoscopy delivery is provided. In general, the delivery catheter 130 consists of a balloon 132, a flexible catheter 133, a soft tip 131, a block ring 134, a flexible shell 135 and a handle 136. Referring FIG.10B, the stent is compressed and loaded between the flexible tube 133 and the cover tube 135. During the operation, the surgeon holds the handle 136 and pulls the cover tube to release the stent. The block ring 134 prevents the retraction of the stent due to friction during the release process. In some embodiments, the procedure is conducted under X-ray. The radio marker shows the position of the stent under the X-ray image. In some embodiments, the delivery catheter includes a small camera located at the head of the flexible tip. With the illuminance of LED arrays around the camera, it provides an endoscopic view for the operation, which avoids exposure to ionizing radiation and also increases the success rate of the delivery procedure in the dark in vivo environment.EXAMPLE 6

[0105] Referring to FIG. 11, an alternative design of the wireless electrical stimulator 200 is provided. FIG. 11A shows top view of said wireless electrical stimulator. It comprises a flexible or soft substrate 201, printed receiver coils 202, electronic components 203, a printed antenna 204 for wireless communication. In some embodiments, it may further comprise a pressure sensing module 205 and / or a rechargeable battery 206. FIG. 11B shows bottom view of said wireless electrical stimulator. It further comprises another part of the printed receiver coil 202, one or more electrical stimulation electrodes 207-1 and a reference electrode 207-2. In some embodiments, it may further comprise one or more electrical sensing electrodes 208.

[0106] In some embodiments, said electronic components 203 contains a micro controller for processing data from sensors, controlling stimulation module, and wireless communications via radio frequency protocols.

[0107] Referring to FIG.12A, B, related delivery tool 160 is generally provided. It comprises a soft tip 162 and a transparent holder 161. Said delivery tool is designed to assemble with a standard endoscope 150 as shown in FIG. 12C for minimally invasive transoral delivery.EXAMPLE 7

[0108] Referring to FIG. 13, an endoscopy procedure for the minimally invasive implantation is also disclosed. In some embodiments, said wireless electrical stimulator 200 is implanted inside the esophagus for the treatment of gastroesophageal reflux disease (GERD). As shown in FIG. 13A, a submucosal tunnel is created firstly. The endoscopy 150 is inserted through the esophagus 140. An initial incision 141 will be created in the internal lining of the esophagus. This permits entry of the endoscope within the wall of the esophagus, where the muscle will be exposed. In FIG. 13B, the electrical stimulator 200 will be carried by said delivery tool 160 and implanted said tunnel 141 between the muscle layer and the mucosal layer. The exposed electrodes direct contact with the esophageal muscle for effective electrical stimulation. At the end of the procedure, the esophageal incision will be closed with endoscopic clips 170 as shown in FIG.13C.EXAMPLE 8

[0109] Related applications for the wireless electrical stimulation system and endoscopy delivery procedures are also provided. The natural orifice includes but not limited to gastrointestinal tract, urinary tract, trachea, vagina, and etc. In some embodiments, the electrical stimulator is implanted in the esophagus for the treatment of GERD. In some embodiments, the electrical stimulator is implanted in the stomach for the treatment of obesityor gastroparesis. In some embodiments, the electrical stimulator is implanted in the small intestine for the treatment of irritable bowel disease. In some embodiments, the electrical stimulator is implanted near the anal sphincter for the treatment of faecal incontinence. In some embodiments, the electrical stimulator is delivered through the urinary tract and implanted in the bladder for the treatment of urinary incontinence. In some embodiments, the electrical stimulator is delivered through the vagina to restore the normal functions of the pelvic floor muscles.

Claims

What is claimed is:

1. A system for stimulating a target tissue with electrical signals, comprising: a. A wireless power transfer module configured to operate at a resonant frequency, comprising one or more wearable transmitter coils and a portable control circuit; and b. A wireless and deformable electrical stimulator configured for placement into a subject and operating at said resonant frequency, comprising at least one receiver coil, a power management module and a stimulation module; wherein said wireless power transfer module generates an alternative magnetic field which is passed through said at least one receiver coil to induce an alternative voltage which is converted to a stable voltage by said power management module to power said stimulation module to generate said electrical signals.

2. The system of claim 1, wherein said portable control circuit comprises: a. a rechargeable battery, a power management circuit providing constant currents and different voltages, a pulse width modulation generator, a full-bridge inverter, metal-oxide-semiconductor field-effect transistor (MOSFET) drivers; and one or more matching capacitors; or b. a rechargeable battery, a power management circuit, a signal generator, a power amplifier, and an antenna auto tuner configuring said one or more wearable transmitter coils operating at said resonant frequency.

3. The system of claim 1, wherein said resonant frequency ranges from 100k Hz to 1G Hz.

4. The system of claim 1, wherein said electrical signals comprise: a. monophasic or biphasic voltage pulse or pulse train; or b. monophasic or biphasic current pulse or pulse train; or c. charge balanced current pulse or pulse train.

5. The system of claim 1, wherein said electrical signals comprises one or more set of parameters selected from the group consisting of: a. a current amplitude ranging from 3 mA to 15 mA; b. a frequency ranging from 1 Hz to 1000 Hz; and c. a pulse width ranging from 100 microseconds to 200 milliseconds.

6. The system of claim 1, wherein said stimulation module comprises one or more electrodes for delivering said electrical signals into said target tissue.

7. The system of claim 1, wherein said one or more electrodes comprises one or more characteristics selected from the group consisting of: a. said one or more electrodes are needle-shaped;b. each of said one or more electrodes are separated by 0.1 mm to 30 mm; and c. said one or more electrodes has a length ranging from 50 um to 300 um.

8. The system of claim 1, wherein said power management module comprises a rectifier circuit for converting said alternative voltage to said stable voltage, wherein said rectifier circuit is selected from the group consisting of: a. a plurality of diodes and capacitors; b. A full-bridge rectifier; c. A linear low dropout regulator; d. A boost converter to increase said stable voltage; and e. A buck converter to decrease said stable voltage9. The system of claim 1, wherein said wireless and deformable electrical stimulator is adapted for placement into said subject via a natural orifice selected from the group consisting of gastrointestinal tract, trachea, urinary tract, and vagina.

10. The system of claim 1, wherein said wireless and deformable electrical stimulator further comprises a microcontroller configured to perform one or more functions selected from the group consisting of: a. set parameters of said electrical signals; b. control said stimulation module; and c. process data for wireless communication via radio frequency protocols.

11. The system of claim 1 , wherein said wireless and deformable electrical simulator further comprises a sensing module configured to monitor movement or pressure inside said subject.

12. The system of claim 1, wherein said wireless and deformable electrical stimulator further comprises one or more sensing electrodes configured to measure electrophysiological signals of said target tissue.

13. The system of claim 1, wherein said one or more wearable transmitter coils are selected from the group consisting of a single solenoid, a planar coil, a pair of Helmholtz coils, a pair of solenoid coils braided by a single wire, and a planar coil with an additional resonator coil configured to operate at same resonant frequency.

14. The system of claim 1, wherein said wireless and deformable electrical stimulator further comprises a mechanical skeleton; said at least one receiver coil is an elastic coil braided along said mechanical skeleton.

15. The system of claim 14, wherein said wireless and deformable electrical stimulator is made of materials allowing said electrical stimulator to be stretchable up to 50%.

16. The system of claim 15, wherein said materials comprise dielectric materials for substrates and encapsulation; and intrinsic conductive materials for circuit traces and contact pads; wherein a. said dielectric materials are selected from the group consisting of poly dimethylsiloxane (PDMS), polyurethane (PU), styrene ethylene butylene styrene (SEBS), polyimide (PI), polyethylene terephthalate (PET) and hydrogels; b. Said intrinsic conductive materials are selected from the group consisting of silver nanowires, carbon nanotubes, gold nanowires, poly(3,4- ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), printed copper wire and gallium-based liquid metal.

17. A method for delivery of said system of claim 1 to said target tissue, comprising the steps of: a. Inserting a delivery tool through an opening to a desired location, said delivery tool comprises a balloon and a stent compressed within said delivery tool; said stent is integrated with said wireless and deformable electrical stimulator; b. Releasing said stent integrated with said wireless electrical stimulator; and c. Inflating said balloon so that said stimulation module contacts said target tissue.

18. The method of claim 17, wherein said opening is a natural orifice selected from the group consisting of gastrointestinal tract, trachea, urinary tract, and vagina.

19. The method of claim 17, wherein said delivery tool further comprises a flexible shell, a soft tip, a block ring, and a balloon with a flexible catheter.

20. A method for delivery of said system of claim 1 to said target tissue, comprising the steps of: a. Creating a submucosal tunnel between a mucosal layer and a muscle layer by a standard endoscope; b. Assembling said wireless and deformable electrical stimulator with a delivery tool connected with said standard endoscope; c. Inserting said wireless and deformable electrical stimulator into said submucosal tunnel; d. Configuring said wireless and deformable electrical stimulator to deliver electrical signals to said target tissue; and e. Closing said submucosal tunnel.

21. The method of claim 20, wherein said delivery tool comprises a soft tip, and a transparent holder configured to connect said wireless electrical stimulator and a standard endoscope.

22. The method of claim 20, wherein said target tissue is a muscle layer in the gastrointestinal tract, urinary tract, or reproduction system.

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