Wireless multipoint electrical microstimulation system and related methods

Abstract

A wireless multipoint patterned electrical microstimulation system is described, featuring a network of miniaturized wireless microchips designed for epicortical implantation. Each microchip includes a wireless energy harvesting module, an energy conversion module, and integrated electrodes for focal tissue stimulation. The system utilizes a wireless communication module to manage stimulation parameters such as amplitude, pulse duration, and repetition rate. The wireless energy source is an external radio-frequency source, and the microchips are sub-millimeter in size, delivering biphasic current. The communication protocol is a prescheduled, collision-free bitmap protocol with sub-millisecond latency, allowing for targeted stimulation of specific cortical areas. The system is suitable for chronic implantation in motor and sensory cortical areas of freely moving animals, such as rats, to study the effects of patterned intracortical electrical stimulation on behavior, while maintaining safety limits on wireless energy power.

Description

Wireless Multipoint Electrical Microstimulation System and Related MethodsBACKGROUNDField

[0001] The present disclosure relates to a wireless multipoint patterned electrical microstimulation system, and more particularly, to a system utilizing a network of implanted silicon microchips which deliver precisely space-time controlled stimulus to an organ in the body such as for targeted cortical stimulation.Description of the Problem and Related Art

[0002] Brain-computer interfaces (BCIs) and related electronic biomedical interfaces represent a rapidly evolving field that seeks to establish direct communication pathways between the brain and external electronic devices, and similarly between physiological circuits and electronic devices. This technology holds the promise of revolutionizing the way we interact with machines, offering new possibilities for individuals with disabilities, enhancing human capabilities, and providing deeper insights into brain function. A significant challenge in the development of BCIs is the ability to not only record neural activity but also to deliver precise and meaningful stimulation to the brain. This is particularly important for creating closed-loop systems where the brain can both send and receive information in real-time.Traditional methods of neural stimulation, such as deep brain stimulation and surface stimulation, have been instrumental in treating various neurological conditions and in mapping brain functions. However, these methods are limited in their ability to provide targeted stimulation across multiple areas of an organ such as the brain. The need for a more refined approach has led to the exploration of wireless and minimally invasive technologies that can offer greater flexibility and scalability. The development of wireless microstimulation systems aims to overcome the limitations of existing technologies by providing a means to deliver targeted electrical stimuli across large functional targets such as specific cortical areas by external control of the amplitude of the stimulus current, the pulse duration, and repetition rate for eachautonomous microchip across an ensemble of implants. This approach not only enhances the potential for therapeutic applications for neurological disorders but also opens new avenues for research into the complex dynamics of brain and other organ activity such as cardiac circuits.SUMMARY

[0003] For purposes of summary, certain aspects, advantages, and novel features are described herein. It is to be understood that not necessarily all such advantages may be achieved in accordance with any one particular embodiment. Thus, the apparatuses or methods claimed may be embodied or carried out in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other advantages as may be taught or suggested herein.

[0004] The system may enable wireless physiological stimulation at numerous independent locations such as across the brain cortex. The system can include an external wireless hub that may transmit an RF impulse, which can serve as a downlink signal. A network of microchips may receive the RF impulse and convert the energy into a stimulation response. This response can be imparted to physiological tissue either directly as electrical excitation or indirectly through conversion by an integrated transducer into optical, acoustic, electrochemical, or thermal stimuli by each microchip.

[0005] The network of microchips may be arranged in a wireless serial mapping topology, e.g., a daisy chain network, allowing for efficient and fast communication and control.

[0006] Each microchip in the system may include an energy harvesting circuit that can convert energy from the RF impulse into power for the microchip.Additionally, a demodulator may be present to demodulate the downlink signal, and a controller can manage the microchip's operations.

[0007] The microchips may be extremely small, with each being a fraction of a millimeter in size, allowing for minimal invasiveness and precise application.

[0008] The downlink signal in the wireless serial mapping topology can program each chip in less than 10 microseconds, ensuring rapid actuation and adaptability across a large ensemble of chips.

[0009] The impulse downlink signal may include a 1 -bit to 10-bit command unique to each microchip. This command can generate a response embodying stimulation parameters, which may include amplitude, pulse width, and repetition rate.

[0010] The impulse downlink can be kept off and only used for the duration of the stimulus to maintain the RF transmission and stimulation duty cycle at 10% or less. This feature may help limit RF exposure to the body, enhancing safety.

[0011] A method for stimulating physiological tissue with the system may involve transmitting an impulse downlink of less than 10 microseconds in duration. The method can include harvesting energy from the impulse downlink, processing the impulse downlink to retrieve a command signal, and delivering a stimulation response into the tissue based on the command signal.

[0012] The network of microchips in the method may comprise up to 1000 or more microchips arranged in a wireless serial mapping topology, allowing for extensive coverage and control.BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The apparatus / system / method is described with reference to the accompanying drawings. In the drawings, like reference numbers indicate identical or functionally similar elements. Additionally, the left-most digit(s) of a reference number identifies the drawing in which the reference number first appears.

[0014] FIG. 1 shows an exemplary wireless multipoint electrical microstimulation system implanted in a subject;

[0015] FIG. 2 is a functional schematic of an exemplary external RF hub containing circuits which report wirelessly each stimulation event back to the hub;

[0016] FIG. 3 is a functional schematic of an exemplary microstimulator;

[0017] FIG. 4 is plot of an RF transmission from the external hub and signals derived from it by the microstimulator;

[0018] FIG. 5 is a flowchart showing an exemplary method for using the system of FIG. 1 ;

[0019] FIG. 6A is a plot of exemplary command signals over time against the current they exhibit;

[0020] FIG. 6B is a plot of the total charge for each command signal;

[0021] FIG. 6C is an expanded time axis of the stimulation waveform for a pulse width per phase of 100 ps varying with the transmit power level;

[0022] FIG. 6D is a plot of power levels of the minimum power command and the maximum power command and its effect on oscillator power levels;

[0023] FIG. 6E is a graph of downlink waveforms transmitted at different data rates (0.73 - 1 .26 Msps) and the stimulation event generated as a response to the commands for a particular microstimulator chip;

[0024] FIG. 6F shows the tolerance to a wide range of downlink rates when measured as a range of stimulation frequencies;

[0025] FIG. 6G shows the amplitude of current injection as a function of transmit RF power;

[0026] FIG. 6H illustrates control of the stimulation frequency directly by downlink transmission frequency;

[0027] FIG. 6I depicts waveforms of the RF downlink and injected stimulation, respectively, demonstrating low duty cycle RF phase; and

[0028] FIG. 6J shows the programmability of a 6 chip population.DETAILED DESCRIPTION

[0029] The various embodiments of the wireless multipoint electrical microstimulation system and method and their advantages are best understood by referring to FIGs. 1 through 6J of the drawings. The elements of the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the novel features and principles of operation. Throughout the drawings, like numerals are used for like and corresponding parts of the various drawings.

[0030] Where used herein and unless specifically indicated otherwise, the following terms are intended to have the following meanings in addition to any broader (or narrower) meanings the terms might enjoy in the art:

[0031] Unless otherwise required by context, the use herein of the singular is to be read to include the plural and vice versa. The term “a” or “an” used in relation to an entity is to be read to refer to one or more of that entity. As such, the terms “a” (or “an”), “one or more,” and “at least one” are used interchangeably herein.

[0032] As used herein, the term “comprise,” or variations thereof such as “comprises” or “comprising,” are to be read to indicate the inclusion of any recited integer (e.g. a feature, element, characteristic, property, method / process step or limitation) or group of integers (e.g. features, element, characteristics, properties, method / process steps or limitations) but not the exclusion of any other integer or group of integers. Thus, as used herein the term “comprising” is inclusive or open- ended and does not exclude additional, unrecited integers or method / process steps.

[0033] Furthermore, reference in the specification to “an embodiment,” “one embodiment,” “various embodiments,” or any variant thereof means that a particular feature or aspect described in conjunction with the particular embodiment is included in at least one embodiment. Thus, the appearance of the phrases “in one embodiment,” “in another embodiment,” or variations thereof in various placesthroughout the specification are not necessarily all referring to its respective embodiment.

[0034] As used herein, the term "subject" refers to a mammal, including but not limited to a dog, cat, horse, cow, pig, sheep, goat, rodent, or primate. Subjects can be house pets (e.g., dogs, cats), agricultural stock animals (e.g., cows, horses, pigs, chickens, etc.), laboratory animals (e.g., mice, rats, rabbits, etc.), but are not so limited. Subjects particularly include human subjects in urgent treatment as described herein. The human subject may be a pediatric, adult, or a geriatric subject. The human subject may be of any sex.

[0035] This disclosure is directed to a wireless multipoint patterned electrical microstimulation system that may include a spatially distributed network of miniaturized wireless microchips designed for epicortical implantation into a subject. Each microchip may consist of a wireless energy harvesting module that can collect energy from an external radio-frequency source, which is then converted into biphasic stimulation current by an energy conversion module. This current may be injected focally into tissue through a pair of integrated electrodes. The system may also feature a wireless communication module that can control stimulation parameters such as amplitude, pulse duration, and repetition rate across the network using a prescheduled, collision-free bitmap protocol with sub-millisecond latency. The network of microchips may be configured to target specific cortical areas and can be chronically implanted into motor and sensory regions of the cortex in freely moving animals, such as rats. This setup may allow for the demonstration of the effects of patterned intracortical electrical stimulation on trained animal behavior, potentially at average wireless energy powers below safety limits. The system may serve as a platform for exploring neural stimulation therapies and brain-computer interface applications.

[0036] FIG. 1 is an illustration of the system 100 for wireless multipoint electrical microstimulation where a subject S is implanted with a plurality of microstimulators 101a-c in the subject S cortex. The system 100 includes an external antenna coil 105 for relaying RF power and command signals from an external hub 103. Each microstimulator 101 may be an application-specific integrated circuit(ASIC), system-on-chip (SoC). Each chip is a fraction of a millimeter in size. For example, microstimulator 101 may be 300, 400, or 500 pm per side, fabricated in a low-power RF complementary metal-oxide semiconductor (CMOS) process. The number of chips in the network may be up to 1000 microstimulators 101. In some cases, more than 1000 microstimulators 101 may be deployed. In some embodiments, a subdermal relay antenna may be employed, interposed between the external antenna coil and the microstimulator array.

[0037] FIGs. 2 and 3 are functional schematics of an exemplary external hub 103 and an exemplary microstimulator 101. Referring first to FIG. 2, an external hub 103 may include a transceiver which may be a software-defined radio (SDR) 201 which is in communication with an external device 207 (e.g., a control computer) through which a user may configure and input stimulation commands to the external hub 103. Commands are issued from SDR 201 through a power amplifier 205 which provides an amplified signal to through a duplexer 203 to external antenna coil 105 as an outgoing RF command signal 202. External antenna coil 105 converts the outgoing command signal 202 into a downlink signal 206.

[0038] Referring now to FIG. 3, downlink signal 206 is received at a microstimulator 101 through on-chip coil antenna 301 which relays the signal to energy harvest / rectifier circuitry 305. Scavenged RF energy is provided to power circuitry 307 and power-on reset (POR) circuit 309. POR circuit 309 ensures that on- chip system starts up in a known, stable state when power is first applied, monitoring the supply voltage during power-up and holding the system (e.g., microcontroller or processor) in a reset state until the voltage reaches a safe, stable level. Once the voltage is sufficient and stable, the POR circuit 309 deactivates the reset signal, allowing the system to begin normal operation.

[0039] Microstimulator 101 includes a controller 321 , a demodulation circuit 311 , a daisy chain network detector responsive to POR circuit 309, and which are driven by a free-running oscillator 319. Rectified signals 302 are demodulated by demodulation circuit 311 and input as a data signal 304 to daisy chain detector 313. Downlink 206 transmission protocol may be an amplitude-shift-keying-pulse-width- modulation (ASKPWM). ASKPWM has the benefits of efficient data encoding andcontrol where amplitude-shift-keying (ASK) encodes data by varying amplitude (e.g., presence or absence of a pulse) and pulse-width-modulation controls signal characteristics (e.g., power or intensity) through pulse width. Combining both enables simultaneous data and power modulation which makes it ideal for stimulation signal generation and control. It also promotes better signal integrity where PWM helps maintain timing-based information integrity and ASK provides clear high / low states for easy detection. The receiver design may be simpler because the receiver can decode amplitude for binary data and pulse width for control signals, sometimes avoiding the need for separate control lines. Especially in applications like wireless communication or power-efficient transmitters, the combination of ASK and PWM can optimize power use.

[0040] A daisy chain detector 313 in a daisy chain network topology is used to determine whether a particular receiver is the last (or only) device in the chain. It detects the presence or absence of a downstream device (another receiver or node). If no device is connected after it, the detector identifies the receiver as the end of the chain. A receiver might monitor a "pass-through" signal line or a specific pin that loops back only if the next device is present. If the signal is not returned or the voltage level is missing, the detector concludes it's the last device. In this case, The daisy chain detector 313 monitors downlink bits as generated by the demodulator 311 . Upon detecting the proper ‘sync’ sequence, the detector 313 begins counting bits until finding the three bits designated for the specific chip matching its unique address. Then, the digital controller 321 uses these three bits to program the waveform -specific stimulation waveform for the current source driver. Note that as the clock frequency of a chip can be extracted from the received BPSK uplink data, this can be used as an indicator for the power status onboard a chip.

[0041] Data signal 304 is relayed to controller 321 which is configured to extract command information from data signal 304. Command information comprises stimulation parameters that may be varied according to input from computer 207. Stimulation parameters include any of pulse amplitude, pulse width, and repetition rate. Controller 321 encodes command information into a command signal 306 which is issued to a stimulation driver 323 which converts command signal 306 to stimulation impulses 308 according to the stimulation parameters. Stimulationimpulses 308 are coupled to one or more integrated electrodes 303a, 303b (e.g.,) which may be in direct contact with subject S cortical or nervous system tissue, thus imparting the stimulation impulses 308 to the tissue. Alternatively, stimulation impulses may be imparted to subjects indirectly through a suitable transducer such that the stimuli may be any of the following: acoustic, electrochemical, or thermal.

[0042] POR circuit 309 also triggers a modulation circuit 315 to transmit the chip address, received from controller 321 and modulated using, for example, binary phase shift keying (BPSK), through on-chip antenna 301 which converts the address signal to an uplink signal 208. Uplink signal 208 is received by external hub 103 and reported to computer 207. Those skilled in the relevant arts will appreciate that BPSK may be a preferred protocol for the uplink signal because of its efficient bandwidth usage and low bit error rate.

[0043] Downlink signal 206 delivers RF power and commands at 1 Mbps to specific microchips to select one of preprogrammed current waveforms. FIG. 4 shows the waveform of the downlink 206 and uplink 208, rectifier output voltage (Vrect) 302, demodulated downlink bit 304, and stimulation impulses 308. The plot illustrates how the downlink is ‘on’ for a short period of time to deliver RF energy to the chip - only when needed resulting in duty-cycled RF transmission hence lowering average RF exposure. Accordingly, duty cycle of the downlink signal is about 10% or less, thereby limiting RF exposure to the subject S.

[0044] Downlink signal 206 may comprise a 1 -bit to 10-bit command unique to each microchip based on a microcstimulator’s 101 unique address, and downlink signal 206 may be less than 10 ps. Uplink signal 208 may transfer at a rate of up to 10 Mbps.

[0045] FIG. 5 is a flowchart illustrating an exemplary method 500 related to the system described above. At step 501 , a network of microstimulators is implanted in a subject S. A downlink signal 206 is transmitted to one or more of the implanted microstimulators 101 from external hub 103, where the downlink signal 206 comprises a 10 ps command to impart stimuli to subject S tissue according to stimulation parameters, the parameters being any of pulse amplitude, pulse width,and repetition (Step 502). In some embodiments, the downlink signal 206 is modulated according to the ASKPWM scheme.

[0046] The microstimulator 101 harvests power from the downlink signal 206 using on-chip energy harvesting circuitry at Step 503. Concurrently, at Step 504, the downlink signal 206 is demodulated (using the appropriate protocol, e.g., ASKPWM) and information representing the command signal is retrieved and processed by the controller 321 . Controller 321 then inputs the command signal to the stimulation driver to deliver the commanded stimuli to the electrodes 505.EXAMPLE

[0047] As with remote RF powering of active implantable biomedical devices in general and near-field (inductively coupled) harvesting for cortical implants in particular, careful strategy is called to ensure safe RF power delivery. In the case of the spatially distributed microstimulators 101 , chip circuit designs must consider likely variations in the magnetic field across the total implant area and corresponding energy harvesting. The stimulator circuit of FIG. 3 was implemented in silicon dies with sizes of 300, 400, and 500 pm, fabricated in the 65 nm low-power RF CMOS process. Measurements were made as to how chip area (i.e. size of the microcoil antenna on the die) relates to incident Tx power requirements. To maximize the available on-chip charge, an unregulated voltage supply for the overall circuit was used where an overvoltage protection (OVP) diode sets the upper limit of VDD. The Tx power affects the harvested power level as well as the voltage supply so that an increase in Tx power causes an increase in clock frequency of the free-running oscillator 319. In animal experiments, a slightly larger 500 pm size chips were used due to the availability of a larger numbers of chips. However, the above test suggests that even smaller microstimulators can operate in similar fashion albeit with increased Tx power.

[0048] Three-bit commands from the downlink 206 (seven types, 6 types for single shot stimulation, 1 type for continuous 100 Hz stimulation) determine the current amplitude and pulse width of injected current as shown in FIG. 6A, where each command corresponds to delivery of a specified amount of total charge (FIG.6B). Due to the unregulated voltage supply, the current amplitude increases with respect to the incoming RF power as shown in FIG. 6C. However, since the clock frequency also increases with RF power, the stimulation period decreases. In effect, the two effects nearly cancel out whereby increase in injected total charge, e.g., for command 3 is up by only 13.7% despite a tenfold increase in Tx power (inset of FIG. 6C). As an example, FIG. 6D illustrates the total injected charge generated by commands 6 (maximum) and 1 (minimum), respectively. Note that even if the Tx power were to increase tenfold, the increase in maximum charge delivered was measured as 38.8%, demonstrating the moderation of RF power level variations in the circuit design and notwithstanding the choice of a simple unregulated voltage source.

[0049] The choice of a free-running oscillator in the microstimulator offers the benefit of low power consumption and small footprint. Still, wafer-level variations in the CMOS fabrication can lead to clock frequency variance across an ensemble of RF powered devices. The ASKPWM downlink protocol is tolerant of anticipated clock variance; an asset validated by varying the downlink data rate as shown in FIGS. 6E & 6F. The results demonstrate that the ASKPWM demodulator can achieve a 100% success rate provided that the downlink variance is less than 23%, well within the range of observed clock frequency variance. The downlink protocol is quite fast and also microchips to generate a wide range of stimulation frequencies up to 2 kHz even if such frequencies might be well in excess of pulse repetition rates normally used for neuromodulation. Even for such high-frequency stimulation, however, the amplitude of injected pulsed current remains rather constant as shown in Figs. 2g and 2h as determined initially by the Tx power.

[0050] A key feature of the system is the design of a high data rate downlink in a daisy-chain configuration which results in low-duty cycle RF exposure even in the case of a large, distributed chip population. Each downlink event requires only 3 ps for a single chip yet enables stimulation parameters to be programmed across a chip population of any size while keeping overall system latency low. Upon transmitting the three-bit command per chip, the downlink waits until the current is delivered by a given chip and then turns off. Since the effective stimulation period in most neuromodulation schemes is relatively short, RF energy is transferred only for ashort duration keeping the average RF power low and limiting the RF exposure of tissue. FIG. 6I demonstrates such low-duty cycle RF transmission by displaying the 100 Hz 180 biphasic stimulation waveform with 100 ps and 500 ps per phase generated by a downlink at 4.6% and 14% duty cycle, respectively. This short, pulsed downlink command can still control multiple devices simultaneously and reliably, as demonstrated in FIG. 6J with five chips. In this benchtop test example, six different downlink commands are seen to be transmitted sequentially, each command generating preprogrammed values of current amplitudes and durations across the set.

[0051] As described above and shown in the associated drawings, the present invention comprises a wireless multipoint electrical microstimulation system and related methods. While particular embodiments have been described, it will be understood, however, that any invention appertaining to the system and methods described is not limited thereto, since modifications may be made by those skilled in the art, particularly in light of the foregoing teachings. It is, therefore, contemplated by the appended claims to cover any such modifications that incorporate those features or those improvements that embody the spirit and scope of the invention.

Claims

WHAT IS CLAIMED IS:1 . A system for wireless physiological stimulation simultaneously at a large number of independent locations, comprising: an external wireless hub configured to transmit an RF impulse, the RF impulse comprising a downlink signal; a network of microchips configured to receive the RF impulse and convert RF impulse energy into a stimulation response to be imparted to physiological tissue, either as direct electrical excitation or indirectly after conversion by an integrated transducer as optical, acoustic, electrochemical or thermal stimulus by each microchip.

2. The system of Claim 1 , wherein the network of microchips is arranged in a wireless serial mapping topology.

3. The system of Claim 1 , wherein each microchip comprises: an energy harvesting circuit for converting energy from the RF impulse into power for the microchip; a demodulator for demodulating the downlink signal; and a controller.

4. The system of Claim 1 , wherein each microchip is a fraction of a millimeter in size.

5. The system of Claim 1 , wherein the downlink signal in the wireless serial mapping topology programs each chip in less than 10 ps.

6. The system of Claim 5, wherein the impulse downlink signal comprises a 1 -bit to 10-bit command unique to each microchip to generate a response embodying stimulation parameters wherein the stimulation parameters are at least one of amplitude, pulse width, and repetition rate.

7. The system of Claim 1 , wherein the impulse downlink can be turned off to maintain the RF transmission and stimulation duty cycle at 10% or less, thereby limiting RF exposure to the body.

8. A method for stimulating physiological tissue with the system of Claim 1 , the method comprising the steps of: transmitting an impulse downlink to a spatially-distributed network of microchips, the impulse downlink being less than 10 ps in duration; harvesting energy from the impulse downlink; processing the impulse downlink to retrieve a command signal; and deliver a stimulation response into the tissue based upon the command signal.

9. The method of Claim 8, wherein the network of microchips comprises up to 1000 or more microchips arranged in a wireless serial mapping topology.

10. The method of Claim 8, wherein each microchip is a fraction of millimeter in size.11 . The method of Claim 8, wherein the downlink signal comprises 1 to 10-bit command signal unique to each chip across the network to generate a response embodying stimulation parameters wherein the stimulation parameters are at least one of amplitude, pulse width, and repetition rate.

12. The method of Claim 8, wherein the impulse downlink can be turned off to maintain the RF transmission and stimulation duty cycle at 10% or less, thereby limiting RF exposure to the body.

13. A system for physiological tissue stimulation comprising: an external wireless hub configured to transmit an impulse downlink of less than 10 ps in duration, the impulse downlink representing a unique 1-bit to 1 O-bit command to generate a unique response, the response embodying variable stimulation parameters comprising at least one of pulse amplitude, pulse width, and pulse repetition rate, the downlink signal having a duty cycle less than 10% to reduce RF exposure to body; a network of individually addressed microchips configured to receive RF energy from the impulse downlink and to generate the response, each microchip being a fraction of a millimeter in size and comprising: an energy harvesting circuit for converting energy from the impulse downlink into power for the microchip; a demodulator for demodulating the impulse downlink; and a controller; and wherein the network of microchips comprises a wireless serial mapping topology.

Images