WO2017139605A1

WO2017139605A1 - Systems and methods for coordinated neurostimulation with distributed micro particles

Info

Publication number: WO2017139605A1
Application number: PCT/US2017/017410
Authority: WO
Inventors: Anil Kumar Ram RAKHYANI; Peng CONG; Stephen O'driscoll
Original assignee: Verily Life Sciences, LLC
Priority date: 2016-02-12
Filing date: 2017-02-10
Publication date: 2017-08-17

Abstract

A system for neurostimulation is provided. The system includes a micro particle implantable at a target location and a central controller configured to communicate wirelessly with the micro particle. The micro particle includes a power system configured to receive wireless energy transmission, and an electrode system configured to transmit an electrical pulse for stimulating the target location. The central controller includes a power system configured to wirelessly deliver power to the micro particle, a communication system configured to wirelessly communicate with the micro particle, and a processing system configured to control the power system and the communication system. In some implementations, the central controller is configured to instruct the micro particle to transmit one or more electrical pulses to the target location to stimulate a function of at least one of a limb, an organ, or a body part.

Description

SYSTEMS AND METHODS FOR COORDINATED NEUROSTIMULATION WITH

DISTRIBUTED MICRO PARTICLES

BACKGROUND

Related Applications

[0001 ] This application claims priority to U.S. Provisional Application No. 62/294,446, filed February 12, 2016, which is incorporated herein by reference in the entirety.

Technical Field

[0002] The present disclosure relates generally to the field of

neurostimulation, and more particularly, to systems and methods for coordinated neurostimulation with a micro particle or distributed micro particles.

Background Description

[0003] The nervous system of a human has two main parts: the central nervous system {i.e., the brain and spinal cord); and the peripheral nervous system (i.e. , the nerves that carry pulses to and from the central nervous system). The nervous system controls voluntary and involuntary actions of different body parts (e.g., muscles, limbs, organs, etc.) by transmitting and receiving signals to and from the different parts of the body. When a portion of a vertebrate's nervous system becomes damaged (e.g., by disease or injury) the voluntary or involuntary function of a person's body parts, organs, or metabolic systems may be restricted or a person may experience partial or total paralysis or dysfunction. For those who have suffered nervous system damage, efforts have been devoted to using implanted electrode arrays to sense nerve signals and to stimulate nerves in an attempt to restore function to the effected body parts or organs. Although these efforts in some case have produced some positive results, there is much room for significant advancement in the technology in order to render it functional and viable as a long term solution. For example, the large size of known wired electrodes and arrays, and the wires connecting them to a central controller, limit both the functionality and the suitability of these approaches to many applications. SUMMARY

[0004] The present disclosure is directed to systems and methods for stimulating a function of a limb, organ, or other body part by neurostimulation using one or more micro particles.

[0005] In one aspect, the present disclose is directed to a system for neurostimulation. The system may include a micro particle implantable at a target location and a central controller configured to communicate wirelessly with the micro particle. The micro particle may include a power system configured to receive wireless energy transmission and an electrode system configured to transmit an electrical pulse for stimulating the target location. The micro particle may also include a processing system configured to control the power system and the electrode system. The central controller may include a power system configured wirelessly deliver power to the micro particle and a communication system

configured to wirelessly communicate with the micro particle. The central controller may also include a processing system configured to control the power system and the communication system. The central controller may be configured to instruct the micro particle to transmit one or more electrical pulses to the target location to stimulate a function of at least one of a limb, an organ, or a body part.

[0006] In another aspect, the present disclosure is directed to a method of stimulating a function of a limb or an organ by neurostimulation. The method may include identifying a target location associated with the control of the function to be stimulated and selectively distributing a micro particle into the tissue at the target location. The micro particle may include a power system that receives a wireless energy transmission and an electrode system that transmits an electrical pulse to the target location. The micro particle may also include a processing system that controls the power system and the electrode system. The method may also include selectively delivering power and signals wirelessly to the micro particle from a central controller. The central controller may include a power system that wirelessly delivers power to the micro particles and a communication system that wirelessly

communicates with the micro particle. The central controller may also include a processing system that controls the power system and the communication system.

The method may also include selectively stimulating the target location by transmitting an electrical pulse using the micro particle, which stimulates the function of the limb or the organ. In certain embodiments, the neurostimulation may have no therapeutic effect. For instance, the neurostimulation may be for the sole purpose of detecting the response from selectively stimulating the target location, as discussed further below.

[0007] In another aspect, the present disclosure is directed to a micro particle for coordinated neurostimulation. The micro particle may include a power system configured to receive wireless energy transmission and an electrode system configured to transmit an electrical pulse to a target location. The micro particle may also include a processing system configured to control the power system and the electrode system. The micro particle may be one of a plurality of micro particles distributed, in use, into the tissue of a patient at target locations that control a function of a limb or an organ of the patient, each micro particle may be configured to receive informational signals from a central controller to perform a coordinated neurostimulation that stimulates the function of the limb or the organ.

BRIEF DESCRIPTION OF DRAWINGS

[0008] Fig. 1 is a schematic of a neurostimulation system, according to an exemplary embodiment

[0009] Fig. 2 is a schematic illustration of a central controller, according to an exemplary embodiment.

[0010] Fig. 3 is a schematic illustration of a micro particle, according to an exemplary embodiment.

[001 1] Fig. 4 is an illustration of a nervous system of a human.

[0012] Fig. 5 is an illustration of a pair of neurons of the nervous system of

Fig. 4.

[0013] Fig. 6 is a flow chart illustrating a method of coordinated

neurostimulation, according to an exemplary embodiment. DETAILED DESCRIPTION,

[0014] A micro particle as described herein may be defined as a

submillimeter implantable device, submillimeter device, or implantable device having an average diameter below 500 microns.

[0015] Neurostimuiation as described herein may be defined as the delivery of electricity (e.g., electrical pulses) to a neuron, a nerve ceil, or other target location of the nervous system intended to excite a neuron, a nerve cell, or other target location. The delivery of electricity may excite a nerve cell, for example, by inducing the flow of ions through the nerve cell membrane, which may trigger an action potential.

[0016] Fig. 1 shows a schematic diagram of a coordinated neurostimuiation system 100, according to an exemplary embodiment. System 100 may include a central reader/controller, which will be referred to herein as a central controller 102. System 100 may also include one or more micro particles 104 configured to communicate with central controller 102. System 100 may be configured such that central controller 102 powers the micro particles 104 via wireless energy

transmission. System 100 may be configured to wirelessly communicate with the micro particles 104, via wireless data links 106, without the use of leads as typically used for electrode stimulators. Centra! controller 102 and the micro particles may be configured to send and receive informational signals back and forth, which may include, for example, data, instructions, protocols, configurations, and the like. When the term information or informational signal(s) is used herein this may refer to one or more of the categories of information listed above.

[0017] In some embodiments, system 100 may include a single central controller 102 and a single micro particle 104. In some embodiments, system 100 may include a single central controller 102 and a plurality of micro particles 104. For example, in some embodiments, the number of micro particles 104 that system 100 includes may be 2 to 5, 6 to 10, 1 1 to 15, 16 to 20, 21 to 50, 51 to 100, or more. In some embodiments, system 100 may include multiple central controllers 102 and multiple micro particles 104. The number of central controllers 102 and multiple micro particles 104 may be determined and/or adjusted based on a number of variables, including for example, the body part that is to be stimulated, the function of the body part to be stimulated, the distance between the micro particles 04, the extent of damage to the person nervous system, and the size and power of central controller 102. Although the following description is primarily directed to an embodiment of system 100 having more than one micro particle 104, the description is equally applicable to an embodiment of system 100 having just one micro particle 104, besides the description related to coordination of multiple micro particles 104.

[0018] Fig. 2 shows a schematic of central controller 102, according to an exemplary embodiment. Central controller 102 may include a processing system 108, a communication system 1 10, and a power system 1 12. Processing system 108 may be configured and responsible for controlling the overall operation of central controller 102 and coordinating the operation of the micro particles 104.

Communication system 1 10 may be configured to wirelessly send informational signals to the micro particles 104 and receive informational signals from the micro particles 104. The power system 1 12 may be configured to power the central controller 102 and power the micro particles 104 using wireless energy transmission.

[0019] In some embodiments, central controller 102 may include additional components depending on desired functionality and/ or the needs of the

implementation. By way of example, additional components include data ports, disk drives, a user interface, speaker(s), computer network interface(s), indicator light(s), and/or display. In some embodiments, central controller 102 may also include a wireless network adapter (e.g. , WiFi) and an intelligent signal processor enabling secure data communication with other devices over the wireless network. The configuration of central controller 102 may be also be adjustable using any combination of hardware and software components.

[0020] Processing system 108 of central controller 102 may include one or more processors, including for example, a central processing unit (CPU) 1 14. The CPU 1 14 may include any suitable type of commercially available processor or may be a custom design. Processing system 108 may include additional components, for example, non-volatile memory (e.g., a flash memory 1 16), volatile memory (e.g. , a random access memory 1 18 (RAM)), and other like components, configured to store information (e.g., data, program instructions, protocols, configurations, and the like) to enable the control and overall operation of central controller 102 and the micro particles 104.

[0021 ] Communication system 1 10 may utilize a variety of wireless data transmission methods for communicating back and forth with the micro particles 104 via one or more wireless data links 106 (see Fig. 1). For example, in some embodiments, communication system 1 10 may utilize radio data transmission, Bluetooth, near field communication (NFC), infrared data transmission,

electromagnetic induction transmission, and/or other suitable electromagnetic, acoustic, or optical transmission methods.

[0022] According to an exemplary embodiment, as shown in Fig. 2, communication system 1 10 of central controller 102 may utilize radio data transmission and include a number of components to support such transmission, such as a data encoder 120, a data decoder 122, a transmitter and a receiver or a transceiver 124, and/or an antenna 125. In some embodiments of communication system 1 10 may include two antennas, for example, one receiver antenna and one transmitter antenna. Also, in some embodiments, communication system 1 10 may be configured to transmit and receive data using a plurality of different wireless transmission methods.

[0023] Communication system 1 10 may be configured to establish data links between central controller 102 and the micro particles 104. Communication system 1 10 may be configured to transmit informational signals to the micro particles 104 while simultaneously receiving informational signals from the same or other micro particles 104. Processing system 108 may initiate the transmission of one or more informational signals to one or more of the micro particles 104 by conveying a message to the data encoder 120, which may then provide an encoded message to be transmitted through the antenna 125 via the transceiver 124. Processing system 108 may receive transmitted informational signals from the micro particles 104 when a transmission is received by the antenna 125 via the transceiver 124, which in some embodiments, may be decoded by the data decoder 122. Each micro particle 104 may be uniquely addressed, which may enable central controller 102 to individually communication with each micro particle 104. Unique addressing of the micro particles 104 is described in more detail below. In some embodiments, data may be transmitted without encoding or decoding the data by communication system 1 10. Further, in some embodiments, recognition, pairing, or other signaling techniques may be used in place of addressing for transmitting data to and from micro particles 104.

[0024] Power system 1 12 may be configured to use wireless energy transmission to power the micro particles 104. In some embodiments, power system 1 12 may utilize, for example, inductive coupling, resonant inductive coupling, radio frequency, or the like to wirelessly transmit power.

[0025] According to an exemplary embodiment, as shown in Fig. 2, power system 1 12 may utilize resonant inductive coupling and may include a power source 126, an oscillator circuit 128, and/or a transmitting coil 130. Power source 126 may provide any suitable source of power, such as an AC source or a DC source. In some embodiments, the power source 126 may be, for example, a battery, a capacitor, a photovoltaic array, or the like. Oscillator circuit 128 may be powered by the power source 126 and drive the transmitting coil 130. In some embodiments, the signal from the osciilator circuit 128 may be amplified by a power amplifier 132 which may be coupled through, for example, a capacitor, to the transmitting coil 130. The transmitting coil 130 may be mutually coupled with the receiving coils on the micro particles 104, which will be discussed in more detail below. The coupled coils may transfer electromagnetic energy from the transmitting coil 130 through the body tissue to the receiving coils of the implanted micro particles 104 by way of mutual induction.

[0026] Fig. 3 shows a schematic diagram of an individual micro particle 104, according to an exemplary embodiment. Micro particle 104 may include a processing system 208, a communication system 210, a power system 212, and an electrode system 214. Processing system 208 may control the overall operation of the micro particle 104. Communication system 210 may communicate with central controller 102 by sending and receiving informational signals. The power system 212 may power the processing system 208, the communication system 210, and the electrode system 214 of the micro particle 104. The electrode system 214 may be controlled via the processing system 208 based on informational signals received from the central controller 102. [0027] Processing system 208 may include a processor 216 configured to process, for example, data, instructions, protocols, configurations, and the like. For example, the processor 216 may receive informational signals containing instructions from the central controller 102 and based on the instructions control the operation of the electrode system 214 (e.g. , stimulate nerve or sense nerve pulses).

[0028] Communication system 210 may utilize the same wireless data transmission method utilized by communication system 1 10 of the central controller 102. Communication system 210 may include an antenna 218 and a transceiver 220 to establish wireless communication with central controller 102. In order to minimize the number of components and size of the micro particles 104, antenna 218 and transceiver 220 may both be dual function, for example, each may receive and transmit signals. In some embodiments, communication system 210 may include a separate transmitter and a separate receiver rather than the dual function transceiver 220. Similarly, in some embodiments, communication system 210 may include a separate transmitter antenna and a separate receiver antenna rather than the dual function antenna 218. Although not shown, in some embodiments, communication system 210 may include an encoder and decoder. The encoder and/or decoder may be digital enabling better handling of signal attenuation. In some embodiments, all coding and decoding of the informational signals may be done by the central controller 102.

[0029] The power system 212 for micro particle 104, like the power system 1 12 for central controller 102 may use wireless energy transmission, including, for example, inductive coupling, resonant inductive coupling, radio frequency (RF) link, or the like to wirelessly transmit energy. Power system 212 may utilize the same wireless energy transmission method as power system 1 12 of central controller 102.

[0030] According to an exemplary embodiment, as shown in Fig. 3, power system 212 may utilize resonant indicative coupling. Power system 212 may include a receiving coil 222 that may be mutually inductively coupled to the transmitting coil 130 of central controller 102. In some embodiments, power system 212 may also include a power storage device 224 (e.g., battery, capacitor, or a power cell). The processing system 208, communication system 210, and the electrode system 214 may be powered by the energy received via the receiving coil 222. In some embodiments, power system 212 may also include a ground. Embodiments of power system 212 utilizing an RF link for transmission of power may utilize a different type of antenna, thus eliminating the need for receiving coil 222.

[0031 ] The electrode system 214 may include a single electrode 226 or multiple electrodes. In some embodiments the electrode 226 may function as a cathode (i.e., negative electrode), an anode (i.e., positive electrode), or both (i.e., switch between). Embodiments where the electrode system 214 includes multiple electrodes 226, one electrode may function as a cathode and another electrode may function as an anode. The electrode 226 may function as either a stimulating electrode by transmitting electrical pulses (e.g. , input current or voltage pulses) that excite nerves by inducing a flow of ions through the nerve cell membrane or may function as a sensing electrode by detecting electrical pulses transmitted along the neuron structure (e.g. , axon, axon terminal, dendrites, etc.).

[0032] The one or more electrodes 226 of electrode system 214 may be positioned at one or more locations about the micro particles 104. For example, for a cube shaped micro particle 104, electrode 226 may be position on one side and one or more electrodes may be position on the other sides. For a spherical shaped micro particle 04, one or more electrodes 226 may extend, for example along a portion of the outer surface or in some embodiments the electrode may extend the full circumference around the sphere (e.g.. ring shaped electrode).

[0033] In some embodiments, the orientation and direction electrode 226 is facing may be identifiable on the micro particle 104 and thus the electrode may be oriented during placement such that the electrode touches or faces a target location. In some embodiments, with more than one electrode, after placement of the micro particle 104 the active electrode may be advantageously selectable. For example, the electrode best oriented to stimulate a target location may be selected as the stimulating electrode.

[0034] In some embodiments, the orientation of the electrode 226 relative to a target location may be randomly determined based on the orientation of the micro particle 104 upon placement. For example, some micro particles 104 may be positioned such that the electrode 226 is facing a target location while others may be positioned such that the electrode 226 is not generally facing a target location. In some embodiments, the micro particle 104 may adjust the power of the electrical pulse based on the positioning of the electrode 226 relative to the target location. For example, an electrode proximate to and facing a target location may transmit an electrical pulse at less power than an electrode a distance from and facing away from a target location.

[0035] The electrode system 214 may stimulate a nerve cell or portion of a nerve cell positioned proximate to the micro particle 104 by transmitting one or more electrical pulses. The electrical pulses may vary, for example, in power (e.g., voltage and/or current), amplitude, speed, duration, waveform, and frequency. The power of the electrical pulses may vary, for example, by varying either the voltage and/or current at which the pulses are transmitted. The voltage may vary, for example, from about 10 mV to about 30 mV, about 10 mV to about 40 mV, about 10 mV to about 50 mV, about 20 mV to about 30 mV, about 20 mV to about 40 mV, or about 20 mV to about 50 mV. The range of power by which electrode system 214 may stimulate a nerve cell is less than that of the current electrodes, which may reduce the risk of injury or atrophy to the nerve cell and surrounding tissue.

[0036] Each micro particle 104 may be uniquely addressed. For example, each micro particle 104 may be uniquely electromagnetically addressed. Each micro particle may have a unique identification number that may be programmed into the non-volatile memory, hard coded, or generated during the electrical or mechanical fabrication. As a result of the unique addressing, central controller 102 may send unique informational signals to each individual micro particle 104 by modulating at the unique address. Similarly, central controller 102 may be able to individually identify informational signals received from each micro particle 104. In some embodiments, one or more of the micro particles 104 may have the same addressing so that the same information may be transmitted to multiple micro particles 04 at the same time.

[0037] Fig. 4 shows an illustration of a nervous system 300 of a human subject 302. Nervous system 300 is made up of two main parts: the central nervous system 304, which includes the brain 306 and the spinal cord 308, and the peripheral nervous system 310, which includes the nerves that go from the spina! cord to the arms, hands, legs, and feet. The peripheral nervous system 310 is made up of several nerve systems: the sensory nervous system, the motor nervous system, the somatic nervous system, and the autonomic nervous system. The sensory nervous system includes sensor nerves that send information to the central nervous system 304 from internal organs or from external stimuli. The motor nervous system includes motor nerves that carry information from the central nervous system 304 to organs, muscles, and glands. The somatic nervous system includes somatic nerves that control skeletal muscle as well as external sensory organs. The autonomic nervous system includes autonomic nerves that control involuntary muscles (e.g., cardiac muscles).

[0038] The nervous system 300 is made up of billions of nerve cells, which may also be referred herein as neurons. Fig. 5 is an illustration of two

interconnected nerve cells 312, which may be part of a network of interconnected nerve cells. Nerve cell 312 on the left as illustrated may be characterized as the transmitting nerve cell while nerve cell 312 on the right may be characterized as the receiving nerve cell. Each nerve cell 312, as shown in the Fig. 5, may include among other things, a nucleus 314, a cell body 316, an axon 318, axon terminals 319 and dendrites 320. The dendrites 320 collect electrical signals while the cell body 316 and nucleus 314 integrates the incoming signals and transmits outgoing nerve signals down the axon 318 to the axon terminals 319. The axon 318 may be surrounded by a myelin sheath 317 that facilitates transmission of nerve pulses to the axon terminals 319. The axon terminals 319 may pass the outgoing signal to dendrites 320 of the receiving cell. The electrical signals may be transmitted from the transmitting cell to the receiving cell across one or more synapses 322.

[0039] Nerve signals or pulses, which may also be referred to as action potential, is a coordinated movement of sodium and potassium ions across the cell membrane. The inside of a nerve cell is slightly negatively charged, for example, the resting membrane potential is about -70 to -80 mV. A stimulation (e.g., a

mechanical, electrical, or chemical), which may also be referred to as

neurostimulation, can cause a few sodium channels in a small portion of the membrane to open and the position charge that they carry depolarizes the cell (i.e., makes the inside of the cell less negative). When the depolarization reaches a certain threshold value more sodium channels are opened enabling more sodium flow in and triggers an action potential, in other words, the inflow of sodium ions reverses the membrane potential in that area (i.e., making it positive inside and negative outside). When the electrical potential reaches about +40 mV inside, the sodium channels shut down and let no more sodium ions inside. The developing positive membrane potential causes potassium channels to open and potassium ions leave the cell through the open potassium channels. The outward movement of the positive potassium ions makes the inside of the membrane more negative, repolarizing the cell. When the membrane potential returns to the resting value the potassium channels shut down and potassium ions can no longer leave the cell. This sequence of events occurs in a local area of the nerve cell membrane, but these changes get passed on to the next area of the nerve cell membrane, then to the next area, and so down the entire length of the axon. Thus, the action nerve pulse, nerve signal, or action potential gets transmitted (i.e. , propagated) down the nerve cell and transmitted to other nerve cells through synapses. A typical nerve cell may have thousands of synapses enabling it to communication with thousands of other nerve cells, muscle cells, glands, etc.

[0040] The action potential is often referred to as an "all-or-none" response because once the membrane reaches a threshold, it will depolarize to +40 mV.

Action potentials may be propagated rapidly. For example, typical neurons can conduct 10 to 100 meters per second depending on the diameter of the axon (i.e. , larger axon produce faster propagation). Neurons may vary in size depending on the type of neuron. For example, some neurons have an average diameter of as little as about 5 microns while others may have an average diameter of about 00 microns. Neurons can vary structure and many neurons can be anatomically characterized as unipolar, multipolar, or bipolar.

[0041 ] When a portion of a person's nervous system becomes damaged (e.g. , by disease or injury) the voluntary or involuntary function of a person's body (e.g. , limb or organ) may be restricted or a person may experience partial or total paralysis or dysfunction. System 100 may stimulate a function of a limb or an organ by sending electrical pulses to one or more nerves and in some embodiments sensing nerve pulses from one or more nerves using one or more micro particles 104. The electrical pulses transmitted from the micro particles 104 to the one or more nerves may function as a stimulation that cause the sodium channels to open depolarizing the cell and ultimately triggering a nerve pulse or action potential. The following description refers to the use of a plurality of micro particles 104; however, in some embodiments of system 100 may utilize a single micro particle 104.

[0042] Central controller 102 may be a portable or wearable device that a person may carry with them. The micro particles 104 may be implantable into the tissue of a person or animal. Implantation may be planned or more random. For example, in some embodiments the implantation may be planned such that individual micro particles 104 may be implanted at or proximate to specific nerves or portions of a nerve identified to control or transmit the nerve signals that trigger the function which the system is trying to stimulate. In other embodiments, the general region of the target nerve or nerves may be known, but the micro particles 104 may be more randomly distributed in the region of the nerve or nerves rather than being individually placed at predetermined locations. In some embodiments, as illustrated in Fig. 5, micro particles 104 may be implanted near the dendrites 320, synapses 322, axons 318, or axon terminals 319, of one or more nerve cells 312.

[0043] The micro particles 104 may vary in size. In some embodiments, for example, the average diameter of the micro particle 04 may be about 500 microns to about 400 microns, about 400 microns to about 300 microns, about 300 microns to about 200 microns, or about 200 microns or less. Generally, the micro particles may be about the size of a grain of sand. The minimal size of the micro particles will significantly reduce the likelihood of trauma compared to the larger prior art electrodes currently utilized. For example, prior art nerve cuffs designed to wrap around a peripheral nerve can cause trauma to the target nerve as well as the surrounding nerves during installation and operation due to the large size and complexity of the installation.

[0044] The microscopic size of the micro particles 104 enables more precise and refined placement with respect to the corresponding microscopic nerve cells when compared to other electrodes that are an order of magnitude larger. For example, an electrode that is about 1 millimeter in diameter is 10 times the size of a nerve cell that has an average diameter of 100 microns. Thus, the 1 millimeter electrode covers the entire nerve cell and may even cover portions of neighboring nerve cells, in contrast, the micro particles 104 may be about the same order of magnitude of the nerve cell (e.g., 200 micron micro particle 104 and 100 micron nerve cell 312). Thus, the micro particle may be positioned more precisely in order to stimulate a specific nerve cell or portion of a nerve cell. In some embodiments, a micro particle 104 may be placed at or adjacent a specific portion of the nerve 312. For example, a micro particle may be placed at a dendrite branch or limb or may be placed along an axon 318 or at an axon terminal 319 of a nerve 312. In some embodiments, a micro particle 104 may be placed at or near a synapse 322 connecting two nerves 312. In some embodiments, the relative size of the micro particles 104 may allow placement further down the branches of the dendrites 320 or axon terminals 319. This may allow finer location targeting for stimulation and sensing of nerve pulses.

[0045] More refined placement of the micro particles 104, which

advantageously enables more refined targeting for stimulation and sensing may reduce the potential for inadvertently stimulating nerve cells that were not intended, which in some cases may cause inadvertent function stimulation and other side effects. For example, stimulating the larger fibers of the Vagus nerve as part of treatment for epilepsy could inadvertently stimulate too broadly causing heart arrhythmias. Signals sensed from a larger fiber are also more difficult to interpret because of the number of signals not of interest.

[0046] More refined placement of the micro particles 104 and closer proximity placement to the target nerve or portion of the nerve, in addition to reducing the likelihood for inadvertent nerve cell stimulation, also allows the strength of the electrical pulses transmitted from the micro particles 104 to be reduced. For example, the reduced size of the micro particles 104 allows for placement at closer proximity to the target portion of the nerve cell thereby enabling less power (e.g., voltage or current) to be used to stimulate the cell and trigger an action potential. Coulomb^'s law describes the relationship between distance and current intensity as I = k(i/r²). I = current required; k = constant; i = minimal current; r = distance from nerve. Thus, by reducing the distance from the nerve, the minimal current may be reduced. Reducing the strength of the electrical pulses may be beneficial in some situations because electrical pulses above certain power thresholds can cause atrophy to the neural structures over time. Stimulating the nerve cells and triggering an action potential using less power (e.g., current and/or voltage) can reduce or prevent atrophy of the neural structures proximate to the micro particles.

[0047] System 100 as described herein may be utilized in a variety of methods for treating conditions related to nerve damage or nerve malfunction of humans or other animals. Various methods of utilizing system 100 will now be explained with reference to Fig. 5.

[0048] According to an exemplary embodiment, system 100 may be utilized for a method 400 of stimulating a function of a limb or an organ of a person. Method 400 may be used for treating a person (e.g., a patient) who has or is experiencing loss of function or dysfunction of a limb, organ, or other body part. Method 400 may include identifying one or more target locations of one or more nerve cells that are associated with controlling the lost function, at step 402. The scope of what constitutes a target location may vary. For example, a target location may be a specific nerve cell, a specific portion of a nerve cell (e.g. , dendrite, axon, axon terminal, myelin sheath, or synapse), a cluster of nerve cells, or a region of tissue containing one or more nerve cells. In some embodiments, target locations may be adjacent or proximate to one another, for example, two adjacent nerve cells or an axon and axon terminal of the same nerve cell. In some embodiments, target locations may be a distance apart. In some embodiments, the distance apartment may be, for example, less than, about 5 millimeters, about 10 millimeters, about 15 millimeters, about 20 millimeters, about 25 millimeters, or about 50 millimeters. In some embodiments, the distance apartment may be, for example, greater than, about 5 millimeters, about 10 millimeters, about 15 millimeters, about 20 millimeters, about 25 millimeters, or about 50 millimeters. In some embodiments, the distance between target locations may range from about 0.1 millimeters to about 10 millimeters, about 0.5 millimeters to about 10 millimeters, or about 1 millimeter to about 10 millimeters.

[0049] Next, step 404 of method 400 may include distributing one or more micro particles into the patient (e.g. , the tissue) at the one or more target locations. In some embodiments, distributing the one or more micro particles 104 may include placement of one or more individual micro particles at or in the vicinity of one or more target locations. In some embodiments, distributing the one or more micro particles 04 to a target location may include directing them to a target location (e.g., a region) and within the region the one or more micro particles 104 may be more randomly distributed within the region. In some embodiments, distributing or placement of the micro particles 104 may be aided by imaging guidance. For example, a magnetic resonance (MR) imaging system may be used to provide realtime visual feedback during the distribution or placement of the micro particles.

[0050] The target locations can include the brain or the spinal cord (i.e., the central nervous system), peripheral nerves (e.g. , the vagal nerve, the sciatic nerve), or individual organs at the nerve interface (e.g., the heart, the bladder, the pancreas). The target locations for distribution of the micro particles may include different types of nerves, for example, motor nerves, sensory nerves, or autonomic nerves.

[0051 ] In some embodiments, prior to distributing of the one or more micro particles, method 400 may include initiating a startup of system 100, which may include powering up of the micro particles and testing the wireless communication between central controller 102 and the micro particles 104. In some embodiments, powering up of the micro particles and testing of the wireless communication (i.e., startup) may be conducted after distribution of the one or more micro particles. In some embodiments, startup may be conducted for each micro particle after distribution of each micro particle.

[0052] Once the one or more micro particles are distributed and in position, step 406 of method 400 may include selectively delivering power and information wirelessly to one or more micro particles 104. As described herein, each individual micro particle 104 may be uniquely addressed. Thus each central controller 102 may transmit unique information to each micro particle 104.

[0053] Step 408 of method 400 may include central controller 102 selectively stimulating one or more target locations by one or more of the micro particles 104. Stimulation by the one or more micro particles 104 may trigger and action potential at the target locations, which may propagate down the nerve and on to other interconnected nerves. Central controller 102 may execute a stimulation protocol configured to conduct a coordinated stimulation by one or more of the micro particles 104 at one or more of the target locations. The stimulation protocol may be configured to stimulate (e.g. , restore) a function of a limb, an organ, or other body part of a patient. The stimulations by the one or more micro particles 104 may be coordinated, for example, the stimulations may be simultaneous, the stimulations may be sequenced, or the stimulations may be patterned. In some embodiments, the stimulations may be configured to cascade, for example, central controller 102 may instruct a first micro particle 104 to stimulate a first target location and then instruct a second micro particle 104 to stimulate a second target location and then instruct a third micro particle 104 to stimulate a third target location and so on.

[0054] In some embodiments, method 400 may also include selectively sensing nerve pulses at one or more target locations by one or more of the micro particles, at step 410. Central controller 102 may select which of the micro particles 104 sense nerve pulses and which stimulate nerve pulses. In some embodiments, central controller 102 may selectively instruct one or more micro particles 104 to switch from stimulating to sensing based on a stimulation protocol. In some embodiments, a micro particle 104 may stimulate and sense, for example, by using one electrode 226 to sense and another electrode 226 to stimulate. The nerve pulses may be sensed by one or more of the micro particles 104 and informational signals indicative of the sensed nerve pulse may be transmitted back to the central controller 102.

[0055] In some embodiments, method 400 may include coordinated and repeated stimulation (e.g. , step 408) and sensing (e.g., step 410). For example, method 400 may be utilized to stimulate a nerve pulse at one target location and to sense or measure a response at other nerve or target locations. More specifically, method 400 may include stimulating one or more micro particles triggering nerve pulses and propagation of the nerve pulses, which may then be sensed downstream by one or more of the sensing micro particles 104. This coordinated stimulation and sensing may enable central controller 102 to calculate propagation behavior (e.g. , timing, strength, etc.) of nerve pulses.

[0056] Steps 408 and steps 410 may be repeated and in between steps the stimulation and/or sensing protocol may be adjusted in order to achieve a desired result (e.g. , stimulate a function of an organ or body part) acting as a feedback loop. In some embodiments, method 400 may include selectively adjusting (e.g., increasing or decreasing) the power of one or more micro partic!e stimulations based on the sensed nerve pulses (e.g., the timing of the sensed nerve pulses), in some embodiments, between repeating of steps 408 and steps 410 central controller 102 may rearrange which one or more micro particles 104 may stimulate and which one or more micro particles 104 may sense. In some embodiments, central controller 102 may instruct just a single micro particle 104 to stimulate in order to isolate the response of that stimulation and then central controller 102 may sequentially cycle through the other stimulating micro particles 104 in order to identify the response from the isolated stimulations.

[0057] In addition to reassigning the task of each micro particle, in some embodiments, the characteristics of the electrical pulse used for stimulation may be adjusted. For example, the strength (e.g., voltage and/or current), amplitude, speed, duration, waveform, and frequency of the electrical pulse may be adjusted and the response to the adjustment may be sensed by one or more micro particles 104.

[0058] Although the present disclosure describes the use of system 100 and the corresponding methods primarily in reference to human patients, it is understood that system 100 and the corresponding methods may employed with animals as well.

Claims

A system for neurostimulation, comprising:

a micro particle implantable at a target location, the micro particle

comprising:

a power system configured to receive wireless energy transmission;

an electrode system configured to transmit an electrical pulse for stimulating the target location; and a processing system configured to control the power system and the electrode system; and

a central controller comprising:

a power system configured to wirelessly deliver power to the micro particle;

a communication system configured to wirelessly

communicate with the micro particle; and a processing system configured to control the power system and the communication system;

wherein the central controller is configured to instruct the micro particle to transmit one or more electrical pulses to the target location to stimulate a function of at least one of a limb, an organ, or a body part.

The system of claim 1 , further comprising a plurality of micro particles that, in use, are distributed at one or more target locations.

The system of claim 2, wherein the electrode system comprises an electrode, and wherein the controller is configured to instruct the electrode to selectively stimulate and sense electrical pulses at each of the one or more target locations.

4. The system of claim 2, wherein the electrode system comprise at least two electrodes, and wherein the controller is configured to instruct one of the at least two electrodes to stimulate electrical pulses and the other one of the at least two electrodes to sense electrical pulses at each of the one or more target locations.

5. The system of any of claims 1 to 4, wherein the micro particle is configured to wirelessly transmit informational signals to the central controller indicative of the electrical pulses sensed at the target location.

6. The system of any of claims 2 to 5, wherein the plurality of micro particles are uniquely addressable to enable the central controller to communicate with each micro particle individually.

7. The system of any of claims 2 to 6, wherein the central controller is configured to execute a stimulation protocol that stimulates one or more target locations and sense electrical pulses at one or more target locations.

8. The system of claim 7, wherein the central controller is configured to adjust the stimulations at one or more target locations based on electrical pulses sensed at one or more target locations.

9. The system of any of claims 1 to 8, wherein the target location is a nerve cell and the nerve cell is one of a motor nerve, sensory nerve, or autonomic nerve.

10. The system of any of claims 1 to 8, wherein the target location is an axon, an axon terminal, a dendrite, or synapse of a nerve.

1 1. The system of any of claims 1 to 10, wherein the communication system is configured to utilize at least one of: radio data transmission, Bluetooth, near field communication, infrared data transmission, or electromagnetic induction transmission to wirelessly communicate.

12. The system of any of claims 1 to 1 1 , wherein the wireless energy transmission utilizes resonant inductive coupling.

13. The system of any of claims 1 to 12, wherein the micro particle is about 200 micrometers or less in diameter.

14. The system of any of claims 2 to 13, wherein, in use, the micro particles are distributed to different target locations and the distance between the target locations ranges between about 0.1 mm and about 10 mm.

15. The system of any of claims 1 to 14, wherein, in use, the micro particle is implanted into tissue.

16. The system of any of claims 2 to 15, wherein the controller is configured to instruct the electrode system of one micro particle to stimulate electrical pulses and a different micro particle to sense electrical pulses at each of the one or more target locations.

17. A method of stimulating a function of a limb or an organ by neurostimulation, the method comprising:

identifying a target location associated with the control of the function to be stimulated;

selectively distributing a micro particle into the tissue at the target location, the micro particle comprising:

a power system that receives a wireless energy

transmission; an electrode system that transmits an electrical pulse to the target location; and

a processing system that controls the power system and the electrode system;

selectively delivering power and signals wirelessly to the micro particle from a central controller, the central controller comprising: a power system that wirelessly delivers power to the micro particles;

a communication system that wirelessly communicates with the micro particle; and

a processing system that controls the power system and the communication system;

selectively stimulating the target location by transmitting an electrical pulse using the micro particle, which stimulates the function of the limb or the organ.

18. The method of claim 17, further comprising selectively sensing electrical pulses at the target location using the micro particle.

19. The method of claims 17 or 18, further comprising selectively distributing a plurality of micro particles to a plurality of target locations.

20. The method of any of claims 17 to 19, further comprising executing a

stimulation protocol that stimulates one or more target locations and senses electrical pulses at one or more target locations.

21. The method of any of claims 17 to 20, wherein the target location is an axon, an axon terminal, a dendrite, or synapse of a nerve cell.

22. The method of any of claims 17 to 21 , wherein the micro particle is about 200 micrometers or less in diameter.

23. A micro particle for coordinated neurostimulation, comprising: a power system configured to receive wireless energy transmission; an electrode system configured to transmit an electrical pulse to a

target location; and

a processing system configured to control the power system and the electrode system;

the micro particle being one of a plurality of micro particles distributed, in use, into the tissue of a patient at target locations that control a function of a limb or an organ of the patient, each micro particle configured to receive informational signals from a central controller to perform a coordinated stimulation that stimulates the function of the limb or the organ.

24. A modified nerve to which the micro particle of any one of claims 1 to 16 or 23 is attached, such that the one or more micro particles is in signaling contact with the nerve and so the nerve can be distinguished from the nerve in its natural state.

25. A modified nerve obtainable by stimulating neural activity of the nerve

according to any one of claims 17 to 22.

26. A method of controlling a micro particle of any one of claims 1 to 16 or 23 that is in signaling contact with a nerve, comprising a step of sending control instructions to the micro particle, in response to which the micro particle applies a stimulatory signal to the nerve.