Classifications

• • 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
  • A61N1/36135—Control systems using physiological parameters
  • A61N1/36139—Control systems using physiological parameters with automatic adjustment
• • 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
  • A61N1/372—Arrangements in connection with the implantation of stimulators
  • A61N1/378—Electrical supply
  • A61N1/3787—Electrical supply from an external energy source

Definitions

• Neuromodulation often requires complex devices and methods of treatment, and this complexity may limit the ability to implement neuromodulation in a variety of therapeutic and research situations. Acquisition of biological activity and response to neuromodulation therapy can involve sensors and electrodes that are often prohibitive to use in small animal models and result in designing analogous devices in the animal model and translation to a clinically useful device for human patients.
• a neuromodulation device must include a power subsystem, charging subsystem, communication subsystem, and sensing subsystem; traditionally these devices must apply energy to a subject.
• large batteries have traditionally been required to supply sufficient power and maintain sufficient charge for application of electrical stimulation and operation of the system, since batteries typically do not scale well, and smaller batteries have disproportionally less energy stored in them.
• the batteries often occupy the majority of space within the volume of the implant.
• these devices may be optimizing for safe and effective deployment in human patients in order to minimize adverse impact associated with large and cumbersome neuromodulation devices.
• a neuromodulation device can have a power source that may be configured to be wirelessly charged (e.g., by inductive charging, magnetic coupling, and/or magnetic resonance coupling), one or more sensors configured to obtain one or more biological signals from a subject; a processing unit operably connected to the one or more sensors, wherein the processing unit can be electrically coupled to the power source; and one or more neurostimulators in communication with the processing unit, each of the one or more neurostimulators configured to supply electrical stimulation to anatomy of the subject based on the one or more biological signals obtained by the one or more sensors.
• a power source that may be configured to be wirelessly charged (e.g., by inductive charging, magnetic coupling, and/or magnetic resonance coupling), one or more sensors configured to obtain one or more biological signals from a subject; a processing unit operably connected to the one or more sensors, wherein the processing unit can be electrically coupled to the power source; and one or more neurostimulators in communication with the processing unit, each of the one or more neurostimulators configured to supply
• the power source, processing unit, one or more neurostimulators, and one or more sensors can be contained within a housing less than 3 cm 3 (e.g., 2.5 cm 3 or less, 2.0 cm 3 or less, 1.9 cm 3 or less, 1.8 cm 3 or less, 1.7 cm 3 or less, 1.6 cm 3 or less, 1.5 cm 3 or less, 1.0 cm 3 or less, etc.).
• the neuromodulation device can be implanted into anatomy of the subject.
• the neuromodulation device can be configured to communicate wirelessly with one or more remote devices configured to adjust one or more operation parameters of the device.
• the neuromodulation device further comprises a plurality of stimulation engines, each of the plurality of stimulation engines operably coupled to one or more of the neurostimulators.
• the stimulation engines can be configured to coordinate stimulation via the one or more neurostimulators.
• each of the one or more neurostimulators can be configured to supply electrical stimulation having distinct stimulation characteristics coordinated by one or more of the stimulation engines.
• at least one of the one or more sensors can be selected from the group consisting of a temperature sensor, potentiometer, potentiostat, pressure sensor, inertial measuring unit or other biopotential sensor (e.g., electromyography sensor, electrocardiography sensor, neural sensor, etc.).
• the device can be contained within a housing of 3.0 cm 3 or less (e.g.,
• the device can be entirely contained within a 2.2 cm 3 housing.
• the stimulation supplied by the one or more neurotransmitters can be responsive to a biological signal sensed by the one or more sensors.
• at least one of the one or more sensors can be configured to sense a tachycardic event, wherein the stimulation is configured to reduce a heart rate of the subject.
• At least one of the one or more sensors can be an inertial measurement unit, and wherein the stimulation can be configured to reduce involuntary subject movement associated with a disease state.
• at least one of the one or more sensors can be electrochemical sensor, wherein the stimulation is supplied based on one or more biochemical signals within the subject.
• at least one of the one or more sensors can be configured to sense one or more biomolecules, wherein the stimulation is supplied based on the presence of one or more predetermined biomolecules.
• the stimulation can be supplied based on an adaptive closed-loop regime.
• the device can be configured to operably communicate with one or more nerves (e.g., nerve fibers) and/or one or more muscle fibers, wherein selective stimulation is configured to be supplied to one or more nerves and/or muscle fibers.
• the one or more biological signals can be associated with a disease.
• one or more of the sensors can be configured to obtain one or more neural signals, wherein the processing unit can be configured to interpret the one or more neural signals, and wherein stimulation can be supplied based on the one or more interpreted neural signals.
• at least one of the neurostimulators can be configured to supply electrical stimulation to the vagus nerve.
• the device further comprises a nerve cuff operably connected to the processing unit.
• the one or more neurostimulators can be configured to selectively supply electrical stimulation to one or more nerves based on the tissue morphology.
• neuromodulation device can be configured to be at least partially implanted into a subject, the neuromodulation device comprising a housing less than 3 cm 3 , wherein a processing unit and power source can be contained entirely within the housing, the processing unit operably coupled to one or more neurostimulators configured to supply electrical stimulation based on one or more biological signals sensed by one or more sensors; a computing device configured to communicate with the neuromodulation device configured to receive data from the neuromodulation device based on the one or more biological signals. In some examples, the computing device can be configured to develop one or more stimulation regimes based upon received data. In some examples, the neuromodulation device further comprised a plurality of stimulation engines operably connected to the processing unit and at least one of the neurostimulators. In some examples, the neuromodulator can be configured to be charged wirelessly, e.g., by magnetic resonance coupling.
• the communications subsystem may be configured to transmit more than receive.
• the apparatus may be configured to transmit (e.g., data from the one or more sensors, etc.) so that 85% or more of the communication traffic is transmission from the apparatus (with 15% or less receiving), e.g., 87% or more, 88% or more, 89% or more, 90% or more, 92% or more, 95% or more, etc.
• the apparatus may be configured to transmit more than 90% of the time (e.g., more than 92% of the time, more than 95% of the time, more than 97% of the time, more than 98% of the time, more than 99% of the time, etc.).
• the communications sub-system may be skewed to transmitting, rather than receiving.
• the apparatus may be configured so that the control, or the communications subsystem is configured so that the apparatus “listens” for received commands/data at prescribed times, and/or only after transmitting a signal indicating that it will be “listening” for a received transmission withing a predetermined window of time. This configuration may reduce the power requirements and may optimize the operation of the apparatus.
• a bidirectional neuromodulator device can comprise a housing less than 3 cm 3 ; a power source configured to be wirelessly charged (e.g., by inductive coupling, magnetic coupling, magnetic resonance coupling, etc.); one or more sensors configured to obtain one or more biological signals from a subject; a processing unit operably connected to the one or more sensors, wherein the processing unit can be electrically coupled to the power source; one or more neurostimulators in communication with the processing unit, each of the one or more neurostimulators configured to supply electrical stimulation to anatomy of the subject based on the one or more biological signals obtained by the one or more sensors.
• the housing can be coated with parylene.
• the exterior of the housing can be hydrophobic.
• the neuromodulation device further comprises an amplifier operably connected to the processing unit, the amplifier configured to amplify electrical signals produced by biological processes or signals from any of one or more sensors connected to the system.
• the neuromodulation device further comprises a plurality of stimulation engines configured to produce biphasic stimulation.
• the one or more of the neurostimulators can be configured to supply stimulation at a frequency of at least 10kHz.
• the one or more neurostimulators can be configured to apply current selectively to adjacent biological tissue.
• a method of neuromodulation can comprise implanting a bidirectional neuromodulator having a plurality of stimulation engines configured to coordinate a supply of electrical stimulation based on one or more biological signals; acquiring data from one or more biological signals associated with a subject; coordinating a stimulation regime based on the one or more biological signals; supplying current-mode electrical stimulation with one or more neurostimulators operably coupled to one or more of the plurality of stimulation engines, wherein the electrical stimulation is supplied based on the coordinated stimulation regime and wherein the neuromodulator is substantially contained within a housing less than 3 cm 3 .
• a stimulation engine may include all or a portion of a pulse generator and/or other source of neuromodulation that may be in communication with one or more electrodes for applying neuromodulation to the subject.
• a stimulation engine may include one or more circuits that are configured to drive neuromodulation from one or more (e.g., a pair, a subset, etc.) of electrodes.
• Multiple stimulation engines may be included to allow the application of electrical energy to different electrodes or subsets of electrodes having different properties (e.g., pulse width, pulse duration, frequency, etc.).
• FIG. 1 is an example of a neuromodulation device, as described herein, illustrated with a transparent housing exposing internal components.
• FIG. 2 illustrates an example of a neuromodulation device in a partially expanded view with housing elements separated from one another to expose the internal electronics.
• FIG. 3 shows an example of a neuromodulation device without a housing showing the printed circuit boards, power source, and electronic elements that can be incorporated for sensing and neurostimulation, as described herein.
• FIG. 4 illustrates an example of a loop or system interaction with one or more remote devices communicating with a neuromodulation device, as described herein.
• FIGS. 5 A and 5B illustrate examples of operational architecture of a neuromodulation device, as described herein.
• FIG. 6 illustrates an expanded view of elements comprising an example of a neuromodulation devices, as described herein.
• FIG. 7 shows an example of a housing for a neuromodulation device compared to an example of a neuromodulation device that may be contained within the housing, as described herein.
• FIG. 8 illustrates an example of neuromodulation capabilities presented in a diagram highlighting structural elements related to a charging system and a neuromodulation device, as described herein.
• FIG. 9 is a graphical representation of sensor system examples that can be employed by a neuromodulation device, as described herein.
• FIG. 10 illustrates examples of neuromodulation device placement including multiple neuromodulation devices locatable within a subject.
• FIG. 12 is a diagram illustrating an example of neuromodulation device operation in blood glucose and/or anti-inflammatory stimulation according to examples described herein.
• FIG. 13 is a diagram illustrating an example of neuromodulation device operation in hypotensive stimulation to lower blood pressure according to examples described herein.
• a neuromodulation device can have one or more interventional systems in operable communication with a controller and a power source (e.g., an energy storage device, such as a battery, capacitive storage, etc.).
• a power source e.g., an energy storage device, such as a battery, capacitive storage, etc.
• One or more circuit boards e.g., printed circuit boards or
• the lumen 107 may be configured to facilitate the passage of one or more interventional systems for placement within a subject’s anatomy.
• three PCBs 110 are shown in an arrangement generally co-planar with one another to maximize organizational arrangements of the processor 120, controller 125, power source 115, one or more amplifiers 130, and power source charging system.
• a processor includes hardware that runs the computer program code.
• the term ‘processor’ may include or be part of a controller and may encompass not only computers having different architectures such as single/multi-processor architectures and sequential (Von Neumann)/parallel architectures but also specialized circuits such as field-programmable gate arrays (FPGA), application specific circuits (ASIC), signal processing devices and other devices.
• FPGA field-programmable gate arrays
• ASIC application specific circuits
• a neuromodulation device can have a power source charging system.
• the charging system is configured to charge a battery coupled to a PCB of the neuromodulation device.
• An example of a power source charging system can be a wireless charging means (e.g., a magnetic resonance charging system).
• the neuromodulation device can have a power receiving device configured to wirelessly receive power configured to charge the neuromodulation device power source.
• a power receiving device can be one or more wireless power receiving coils configured to receive power from one or more wireless power transmission devices having one or more transmission coils configured to remotely charge the neuromodulation device power source.
• the magnetic resonance charging system can be configured to wirelessly transfer power to the energy storage device (e.g., a rechargeable battery) of a neuromodulation device.
• the quantity of power transmission coils of the magnetic resonance charging system may be greater than, less than, or equal to the quantity of power receiving coils in operable communication with the neuromodulation device power source.
• a wireless charging system described herein can have four coils, where the wireless power transmitter and the wireless power receiver each comprise two coils.
• a wireless power transmitter can have a coil driven by a signal source that can be inductively coupled to one or more tunable resonant coils. The resonant coils can be tuned using one or more capacitors.
• the wireless power receiver can have one or more tunable resonant coils that can be inductively coupled to a load coil.
• the load coil can be electrically connected to the neuromodulation device electronic circuitry (e.g., one or more PCBs).
• a wireless charging system for a neuromodulation device can have an operation frequency between 0.01 and 10 MHz.
• an operation frequency of a neuromodulation device operation frequency can be between 5MHz and 8MHz.
• an operation frequency of a wireless charging system for a neuromodulation device can be 6.78MHz.
• a neuromodulation device and wireless charging system described herein may be deployed in an animal (e.g., a mouse).
• a wireless charging system described herein can have one or more coils (e.g., two coils) on the transmission device that can be wrapped around a box configured to receive or house a mouse cage.
• a neuromodulation device associated with mice inside of the cage can receive wireless power transmitted from the one or more coils and received by the power receiving coils of the neuromodulation device.
• FIG. 2 a neuromodulation device is illustrated with two halves of a housing 105 separated from one another exposing the electrical components of the neuromodulation device 100.
• Multiple PCBs 110 are shown with the processor 120, power source 115, and additional elements associated with the neuromodulation device function.
• the housing lumen 107 can be seen without an interventional element passing therethrough.
• FIG. 3 shows the neuromodulation device without the housing.
• the transmission system is a wireless communication system configured to transmit data to and from the neuromodulation device in real-time.
• the wireless communication system can include packaging and transmission of packaged data at a rate sufficient for monitoring biometric data, response to application of neuromodulation device operations, and/or information for development of a treatment or operation regime.
• interventional systems of a neuromodulation device can be an electrical stimulation system having one or more electrodes configured to supply electrical stimulation to a subject.
• the electrical stimulation system may include a plurality of electrodes operably coupled to the controller and in communication with anatomy of the subject, may extend from within the housing to contact or communicate with anatomy of a subject.
• the electrodes can be in operable communication with a controller configured to direct application of an electrical stimulation according to a stimulation regime.
• the electrodes may be configured to contact one or more nerves of a subject.
• one or more electrodes may be a nerve cuff electrode.
• one or more electrodes can be chronic ECG electrodes.
• a stimulation regime may be predetermined and application of electrical stimulation by the one or more electrodes can be stored within the neuromodulation device.
• a predetermined stimulation regime can be transmitted from one or more remote devices in communication with the neuromodulation device.
• the stimulation regime can include electrical stimulation attributes.
• a stimulation regime may comprise intensity, duration, and/or stimulation distribution pattern.
• interventional systems of a neuromodulation device can be a biochemical system including one or more biochemical sensors configured to sense biometric data associated with biochemical molecules within the subject.
• a glucose monitoring sensor may be operably coupled to a neuromodulation device and configured to sense biometric data related to glucose levels in one or more biological tissues.
• a neuromodulation device may supply electrical stimulation and/or may be triggered to release one or more therapeutic compounds to the subject from the neuromodulation device.
• interventional systems of a neuromodulation device can be a biopotential system with one or more sensors configured for electroencephalogram (EEG), electrocardiogram (ECG) and electromyogram (EMG) signal monitoring.
• EEG electroencephalogram
• ECG electrocardiogram
• EMG electromyogram
• the one or more biopotential sensors can be configured to trigger operation of the neuromodulation device to provide stimulation according to the sensed biopotential signals.
• a conformal coating (e.g., parylene C) layer can be added during the encapsulation process. Additional silicone may be added near the electrical feedthroughs (e.g., housing lumen) as a strain relief.
• a mesh e.g., polyester mesh
• an anchor e.g., an anchor point for sutures
• FIG. 6 illustrates an expanded view of a neuromodulation device 100.
• the neuromodulation device includes a power source (e.g., lithium-ion rechargeable battery) 115.
• a power source e.g., lithium-ion rechargeable battery
• Pins 600 can be seen extending upward from the flex PCB to the additional PCBs.
• FIG. 7 is an image of a neuromodulation device outside of a housing 105.
• the housing has a first half and second half coupled to one another at a joint 700.
• the housing lumen 107 is shown at the terminal end of one of the housing halves.
• the neuromodulation device electrical components are removed from the housing to illustrate the size comparison between the electrical components and the housing design.
• the housing design and characteristics can be associated with the dimensions of the neuromodulation device electrical components through one or more methods described herein.
• parts of the housing may engage one another at a joint.
• a joint between housing parts may be a butt joint or lap joint.
• the apparatus may be packaged in an inert configuration.
• the neuromodulation device electronics can be wrapped with polyimide tape (total thickness of 38 microns) prior to packaging.
• the polyimide tape can be configured to to prevent contamination of the electronic components.
• the neuromodulation devices described herein may be implanted within a subject such that the housing and internal systems are located at a site within a subject’s anatomy. Implantation and placement of a neuromodulation device may be related to the target anatomical structures for application of interventional impact of the neuromodulation device.
• intervention for peripheral neuromuscular stimulation can include implantation of a neuromodulation device at or near a peripheral nerve of a subject.
• FIG. 8 illustrates a schematic overview of examples of structures associated with a neuromodulation device. Here, a mouse is depicted and the neuromodulation device 100 is represented as being implanted in the mouse.
• Examples of components for a wireless charger are graphically represented as well as examples of components of the neuromodulation device including the wireless charging system, and computing engine in communication with the interventional systems and sensors.
• An example of a neuromodulation device PCB arrangement can be two component boards (a first PCB and a second PCB) connected by pin connectors (e.g., 16 pin mol ex mezzanine connectors) having signal and power lines.
• An additional flex PCB coil can be connected to the second PCB using pin connectors.
• Such a configuration can provide improved disassembly and augmentation of the neuromodulation device.
• laser cut ferrite sheets can be used to block eddy current build up in other metal components that would decrease the efficiency of the power transfer.
• FIG. 9 illustrates examples of functional modules (e.g., interventional systems) of a neuromodulation device.
• the sensors and/or interventional systems described herein may be physically coupled to the neuromodulation device.
• one or more of the interventional systems and/or sensors may be in wireless communication with a neuromodulation device.
• one or more sensors and/or interventional systems may be locatable at a position or location of a subject’s anatomy separate from the neuromodulation device housing.
• FIG. 14 illustrates an example of a neuromodulation device operation for behavioral conditioning.
• a neuromodulation device described herein can be configured to selectively stimulate target biological tissue (e.g., selective fiber stimulation).
• the diagram illustrated in FIG. 14 shows a process including a neuromodulation device configured to operate separate from one or more sensors.
• electrical stimulation may be selectively applied or applied on-command without need for biometric data from one or more sensors.
• one or more sensors may be used to trigger operation (e.g., neurostimulation) by the device.
• the sensors may be operable to acquire data in response to the manual application of electrical stimulation.
• the neuromodulation device may be controllable by a subject for application of stimulation or other interventional system as desired. As illustrated in FIG.
• the computing devices and systems described and/or illustrated herein broadly represent any type or form of computing device or system capable of executing computer-readable instructions, such as those contained within the modules described herein. In their most basic configuration, these computing device(s) may each comprise at least one memory device and at least one physical processor.
• the term “memory” or “memory device,” as used herein, generally represents any type or form of volatile or non-volatile storage device or medium capable of storing data and/or computer-readable instructions. In one example, a memory device may store, load, and/or maintain one or more of the modules described herein.
• RAM Random Access Memory
• ROM Read Only Memory
• HDD Hard Disk Drives
• SSDs Solid-State Drives
• optical disk drives caches, variations or combinations of one or more of the same, or any other suitable storage memory.
• processor or “physical processor,” as used herein, generally refers to any type or form of hardware-implemented processing unit capable of interpreting and/or executing computer-readable instructions.
• a physical processor may access and/or modify one or more modules stored in the above-described memory device.
• the method steps described and/or illustrated herein may represent portions of a single application.
• one or more of these steps may represent or correspond to one or more software applications or programs that, when executed by a computing device, cause the computing device to perform one or more tasks, such as the method step.
• computer-readable medium generally refers to any form of device, carrier, or medium capable of storing or carrying computer-readable instructions.
• Examples of computer-readable media comprise, without limitation, transmission-type media, such as carrier waves, and non-transitory-type media, such as magnetic- storage media (e.g., hard disk drives, tape drives, and floppy disks), optical -storage media (e.g., Compact Disks (CDs), Digital Video Disks (DVDs), and BLU-RAY disks), electronic-storage media (e.g., solid-state drives and flash media), and other distribution systems.
• transmission-type media such as carrier waves
• non-transitory-type media such as magnetic- storage media (e.g., hard disk drives, tape drives, and floppy disks), optical -storage media (e.g., Compact Disks (CDs), Digital Video Disks (DVDs), and BLU-RAY disks), electronic-storage media (e.g., solid-state drives and flash media),

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• 2023
  • 2023-11-17 EP EP23892651.3A patent/EP4601736A4/de active Pending
  • 2023-11-17 WO PCT/US2023/080266 patent/WO2024108110A2/en not_active Ceased

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