Pulse Generation and Stimulation Engine System

Abstract

The neuromodulation device configured to operate in multiple waveform generation modes includes a power source, a control unit in communication with the power source, a bipolar current generator in communication with the control unit and an input of the switching unit, and a plurality of electrodes. Each electrode communicates with a unique output of the switching unit. The switching unit can provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit. The current generator can deliver an alternating current to at least one working electrode during a first waveform generation mode and a direct current to the working electrode during a second waveform generation mode. The indifferent electrode provides a return path for the alternating current, the direct current, or both. The control unit is configured to detect at least one fault event and prevent, modify, or stop operation of the bipolar current generator in response to the detected at least one fault event.

Description

[Technical field]

[0001] The present application relates in some embodiments to facilitating the blocking, modulation, or attenuation of biological signals passing through neural tissue, including biological tissue processing in nervous system tissue, cardiac tissue, or other voltage-sensitive tissue. [Background technology]

[0002] The gate control theory of pain was developed in the 1960s and led to the emergence of stimulation-based pain management therapies that reduce pain input reaching the brain by selectively stimulating non-nociceptive fibers in the spinal cord to inhibit the transmission of pain stimuli to the brain (see Mendell, Constructing and Deconstructing the Gate Theory of Pain, Pain, February 2014 155(2):210-216). Current stimulation systems for spinal cord stimulation (SCS) that operate on this gate control theory to indirectly reduce pain rely on stimulation signals in the sub-100 Hz frequency range and more recently in the kHz frequency range. Stimulation of the dorsal root ganglion (DRG) in a similar frequency range has also been used to reduce segmental pain through the same mechanism.

[0003] However, the technology based on this premise has drawbacks such as the inhibition of pain transmission is not complete, and side effects such as paresthesia may be unpleasant for the patient.Therefore, it is desirable to have a system and method for treating pain that more effectively blocks or attenuates pain signal transmission through pain fibers, or reduces the excitability of the neurons that process pain signals, and avoids undesirable side effects, rather than indirectly reducing pain signals by gate-theoretic activation of non-nociceptive fibers.Furthermore, the inhibition or attenuation of nerve tissue or nerve activity not only affects pain, but also plays a role in the management of movement disorders, psychiatric disorders, cardiovascular health, and disease states such as diabetes. Summary of the Invention [Means for solving the problem]

[0004] In one configuration, a neuromodulation device or method is provided having multiple failure modes. In one configuration, a neuromodulation device or method is provided having multiple failure mode detection. In one configuration, a neuromodulation device configured to operate in multiple waveform generation modes includes a power source, a control unit in communication with the power source, a bipolar current generator in communication with the control unit and an input of a switching unit, a plurality of electrodes each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, the current generator configured to deliver an alternating current to at least one working electrode during a first waveform generation mode, the current generator further configured to deliver a direct current to the working electrode during a second waveform generation mode, and an indifferent electrode configured to provide a return path for the alternating current, the direct current, or both, and the control unit configured to detect at least one failure event and prevent, modify, or stop operation of the bipolar current generator in response to the detected at least one failure event. In one configuration, a neuromodulation method includes providing a power source, a control unit in communication with the power source, a bipolar current generator in communication with the control unit and an input of a switching unit, and a plurality of electrodes, each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, delivering an alternating current to at least one working electrode during a first waveform generation mode, delivering a direct current to the working electrode during a second waveform generation mode, detecting at least one fault event, and preventing, modifying, or stopping operation of the bipolar current generator in response to detecting the at least one fault event.

[0005] The fault event may include an actual stimulation current differing from a desired stimulation current, the actual stimulation current being an AC current or a DC current. The fault event may include a monitored current signal from a power supply circuit to a switching unit exceeding an expected amount of current. The fault event may include a real-time determination that at least one of a resistance or capacitance of the at least one working electrode is not equal to an expected resistance or expected capacitance of the at least one working electrode. The fault event may include a real-time determination that a peak-to-peak voltage of the at least one working electrode exceeds an expected voltage of the at least one working electrode. The fault event may include a blocking capacitor not functioning properly.

[0006] The direct current may include an anode current and a cathode current, and the fault event may include the anode current not being (1) equal to the cathode current and (2) opposite in sign to the cathode current. The direct current may include an anode current and a cathode current, and the fault event may include the anode current not being (1) different from the cathode current by less than a threshold amount and (2) opposite in sign to the cathode current. The fault event may include any of the fault events described herein.

[0007] In another configuration, a neuromodulation device or method is provided with fault detection of an electrode switching unit. In one configuration, a neuromodulation device configured to operate in multiple waveform generation modes includes a power source, a control unit in communication with the power source, a bipolar current generator in communication with the control unit and an input of the switching unit, a plurality of electrodes each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, the current generator configured to deliver an alternating current to at least one working electrode during a first waveform generation mode, the current generator further configured to deliver a direct current to the working electrode during a second waveform generation mode, and an indifferent electrode configured to provide a return path for the alternating current, the direct current, or both, and the control unit configured to monitor current flowing in a power supply circuit of the switching unit and deactivate the bipolar current generator if the monitored current violates a threshold condition. In one configuration, a neuromodulation method includes providing a power source, a control unit in communication with the power source, a bipolar current generator in communication with the control unit and an input of a switching unit, and a plurality of electrodes, each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, delivering an alternating current to at least one working electrode during a first waveform generation mode, delivering a direct current to the working electrode during a second waveform generation mode, monitoring a current flowing in a power supply circuit of the switching unit, and deactivating the bipolar current generator if the monitored current violates a threshold condition.

[0008] Violating the threshold condition may correspond to the monitored current exceeding a threshold level. Violating the threshold condition may correspond to the monitored current falling below a threshold level. The switching unit may include a multiplexer. The neuromodulation device may further include a reverse bias diode in communication with at least one output of the switching unit, the reverse bias diode configured to prevent reverse biasing of the switching unit at the at least one output.

[0009] In another configuration, a neuromodulation device and method is provided that involves calibration of the current generator. In one configuration, a neuromodulation device configured to operate in multiple waveform generation modes includes a power source, a control unit in communication with the power source, a bipolar current generator in communication with the control unit and an input of the switching unit, a plurality of electrodes each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, the current generator configured to deliver an alternating current to at least one working electrode during a first waveform generation mode, and the current generator further configured to deliver a direct current to the working electrode during a second waveform generation mode, an indifferent electrode configured to provide a return path for the alternating current, the direct current, or both, and a bipolar current generator calibration unit comprising a calibration load and a calibration load switch, the control unit configured to activate the calibration load switch to direct a current from the bipolar current generator to the calibration load, measure the current directed to the calibration load, and calibrate the bipolar current generator in response to the measured current. In one configuration, a neuromodulation method includes providing a power source, a control unit in communication with the power source, a bipolar current generator in communication with the control unit and an input of a switching unit, and a plurality of electrodes, each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit; delivering an alternating current to at least one working electrode during a first waveform generation mode, and delivering a direct current to the working electrode during a second waveform generation mode; providing a bipolar current generator calibration unit comprising a calibration load and a calibration load switch; activating the calibration load switch to direct a current from the bipolar current generator to the calibration load; measuring the current directed to the calibration load; and calibrating the bipolar current generator in response to the measured current.

[0010] The calibration load may include a resistor. The neuromodulation device may further include a current sensor configured to measure a current directed to the calibration load. Calibrating the bipolar current generator may include adjusting a value of a control signal delivered to the bipolar current generator.

[0011] In another configuration, a neuromodulation device or method with independent trim adjustment is provided. In one configuration, a neuromodulation device configured to operate in multiple waveform generation modes includes a power source, a control unit in communication with the power source, the control unit comprising a power controller and a trimming controller, a bipolar current generator in communication with the control unit and an input of a switching unit, and a plurality of electrodes each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, the current generator providing an alternating current current to at least one working electrode during a first waveform generation mode. the current generator includes a plurality of electrodes configured to deliver a direct current to the working electrode during a second waveform generation mode, and an indifferent electrode configured to provide a return path for the alternating current, the direct current, or both, the power controller is configured to provide a power control signal to the bipolar current generator corresponding to a desired current output level, the trimming controller is configured to provide a trimming signal to the bipolar current generator, and the current generator is further configured to deliver an alternating current in the first waveform generation mode or a direct current in the second waveform generation mode in response to the power control signal and the trimming signal.In one configuration, a neuromodulation method includes providing a power source, a control unit in communication with the power source, the control unit comprising a power controller and a trimming controller, a bipolar current generator in communication with the control unit and an input of a switching unit, and a plurality of electrodes, each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, delivering an alternating current to at least one working electrode during a first waveform generation mode, delivering a direct current to the working electrode during a second waveform generation mode, determining a power control signal corresponding to a desired current output level to the bipolar current generator, determining an adjustment signal to the bipolar current generator, and delivering an alternating current in the first waveform generation mode or a direct current in the second waveform generation mode in response to the power control signal and the adjustment signal.

[0012] The bipolar current generator may include at least one amplifier with first and second terminals, the first terminal in electrical communication with the power controller and the second terminal in electrical communication with the trimming controller.

[0013] In another configuration, a neuromodulation device or method with electrocautery and / or defibrillation protection (or other high voltage or current discharge) protection is provided. In one configuration, a neuromodulation device configured to operate in multiple waveform generation modes includes a power source, a control unit in communication with the power source, a bipolar current generator in communication with the control unit and an input of a switching unit, a plurality of electrodes each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, the current generator configured to deliver an alternating current to at least one working electrode during a first waveform generation mode, and the current generator further configured to deliver a direct current to the working electrode during a second waveform generation mode, an indifferent electrode configured to provide a return path for the alternating current, the direct current, or both, and a protection mechanism configured to prevent electrical damage to the neuromodulation device from energy from an external source. In another configuration, a method includes providing a power source, a control unit in communication with the power source, a bipolar current generator in communication with the control unit and an input of a switching unit, and a plurality of electrodes, each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, delivering an alternating current to at least one working electrode during a first waveform generation mode, delivering a direct current to the working electrode during a second waveform generation mode, and preventing electrical damage to one or more of the power source, the control unit, the bipolar current generator, or one or more of the plurality of electrodes from energy from an external source.

[0014] The external source may be an electrocautery device or a defibrillator. The protection mechanism may include at least one positive temperature coefficient (PTC) device and a Zener diode. The Zener diode may be in electrical series with the at least one PTC device.

[0015] In another configuration, a neuromodulation device or method with electrode parameter sensing is provided. In one configuration, a neuromodulation device configured to operate in multiple waveform generation modes includes a power source, a control unit in communication with the power source, a bipolar current generator in communication with the control unit and an input of the switching unit, a plurality of electrodes each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, the current generator configured to deliver an alternating current to at least one working electrode during a first waveform generation mode, the current generator further configured to deliver a direct current to the working electrode during a second waveform generation mode, and an indifferent electrode configured to provide a return path for the alternating current, the direct current, or both, and the control unit configured to determine at least one parameter of the electrodes in real time and to alter operation of the current generator in response to detecting a change in the at least one parameter of the electrodes that is greater than a threshold amount. In one configuration, a neuromodulation method includes providing a power source, a control unit in communication with the power source, a bipolar current generator in communication with the control unit and an input of a switching unit, and a plurality of electrodes, each in communication with a unique output of the switching unit, the switching unit configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit; delivering an alternating current to at least one working electrode during a first waveform generation mode; delivering a direct current to the working electrode during a second waveform generation mode; determining at least one parameter of the electrodes in real time; and altering operation of the current generator in response to detecting a change in the at least one parameter of the electrodes that is greater than a threshold amount.

[0016] The parameter of the electrode may be a series access resistance (Ra) or a double layer capacitance (Cdl). The control unit may be configured to determine at least one parameter of the electrode in real time by using a test rectangular biphasic current pulse and the potential measured between the working electrode and the indifferent electrode. In some embodiments, the techniques and methods described herein may be performed "offline" or not in real time using the same techniques, methods, and algorithms. The parameter of the electrode may be a series access resistance (Ra) or a periodic peak-to-peak voltage (Vpp). The control unit may be configured to determine at least one parameter of the electrode in real time by using a set of sampled points from the potential measured between the working electrode and the indifferent electrode and the instantaneous stimulation current. The control unit may be configured to use at least one parameter of the electrode to control the device according to any of the methods or examples provided herein.

[0017] The direct current may include an extremely low frequency current. The extremely low frequency current may be less than about 5 Hz, less than about 2 Hz, or less than about 1 Hz. The alternating current source may be a high frequency alternating current. The high frequency alternating current may be at least about 1 kHz, or between about 5 Hz and about 1 kHz.

[0018] The power source may include a battery. The control unit may include a first control unit and a second control unit configured to execute independent algorithms. The neuromodulation device may be configured to measure an offset current when the neuromodulation device is in the second waveform generation mode. The neuromodulation device may be configured to measure a periodic Vpp of at least one working electrode. The neuromodulation device may also include a virtual ground configured to be operably connected to the indifferent electrode, the virtual ground being capable of being set at any level to minimize power dissipation. [Brief description of the drawings]

[0019] [Figure 1]1 is a schematic diagram of an application specific integrated circuit (ASIC). [Diagram 2] FIG. 1 is a schematic diagram of an ASIC using DC and AC discrete approaches. [Diagram 3] FIG. 1 is a schematic diagram of an ASIC adapted to deliver DCs. [Figure 4] FIG. 1 is a schematic diagram of an ASIC adapted to deliver DC using a current source. [Diagram 5] FIG. 1 is a schematic diagram of a system having a current source. [Figure 5B] FIG. 1 is a schematic diagram of a system having a current source. [Figure 6] FIG. 1 is a schematic diagram of a fail-safe hybrid system. [Figure 7] 1 is a table of exemplary mechanisms and mitigations. [Figure 8] 1 is a graph of loss capacity and voltage protection. [Figure 9A] 1 is a graph showing disconnection of a reference electrode. [Figure 9B] 13 is a graph relating to bias removal. [Figure 10] 1 is a graph of stimulus onset versus time in seconds. [Figure 11] FIG. 1 is a schematic diagram regarding HW and FW failsafe. [Figure 12] FIG. 1 is a schematic diagram of an example stimulus engine capable of providing ULF and AC stimulation with a single architecture. [Figure 13] FIG. 1 illustrates one embodiment of a system for protecting against high voltages and / or currents using steering diodes and fast acting positive temperature coefficient devices. [Figure 14] FIG. 14 illustrates the system of FIG. 13 clamping dangerously high voltages to safe voltages below 20V. [Figure 15] 13 is a graph of a measurement of an ultra-low frequency (ULF) waveform (sometimes referred to herein as a DC waveform) for stimulating an ULF lead in vitro that may be generated by the stimulation engine of FIG. 12 operating in DC mode. [Figure 16]13 is a graph of an example AC waveform that may be generated by the stimulation engine of FIG. 12 operating in AC mode. [Figure 17] 13 is a table of mitigation mechanisms that may be included within the stimulus engine of FIG. 12. [Figure 18] FIG. 1 illustrates a square wave inserted at the zero crossing point of an ultra-low frequency (ULF) waveform to enable real-time measurement and calculation of circuit parameters. [Figure 19] FIG. 1 illustrates a method for real-time measurement and calculation of a circuit parameter by utilizing a range of approximate values ​​of the circuit parameter and peak and / or slope calculations. [Figure 20] FIG. 1 illustrates a method for real-time measurement and calculation of circuit parameters by sampling current and voltage at limited points of an extremely low frequency waveform. [Figure 21] FIG. 1 illustrates a method for real-time measurement and calculation of circuit parameters by sampling current and voltage at limited time points in an AC current waveform. [Figure 22] FIG. 2 is a schematic diagram of a reference electrode selector. [Figure 23] 13A-13C are schematic diagrams of various instrumentation amplifiers that may be used to measure various voltages of the stimulation engine of FIG. [Figure 24] FIG. 13 is a schematic diagram of various features of the stimulation engine of FIG. 12, including, inter alia, the current generator, rebalance switch, current settings, and polarity / zero. [Diagram 25] FIG. 25C shows the arrangement of FIGS. 25A and 25B. [Figure 25A] FIG. 1 is a schematic diagram of an adjustable stimulation delivery circuit. [Figure 25B] FIG. 1 is a schematic diagram of an adjustable stimulation delivery circuit. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] The present application relates in some embodiments to internal and external pulse generation and / or stimulation engine systems for facilitating the blocking, modulation, or attenuation of biological signals passing through neural tissue, including biological tissue treatments in nervous system tissue (including, but not limited to, neurons and glial cells), cardiac tissue, or other voltage-sensitive tissue. In some embodiments, either the anodic or cathodic phases, or both the anodic and cathodic phases of a waveform delivered to a patient can have a therapeutic effect on electrically excitable tissue, such as neural tissue.

[0021] In some embodiments, the pulse generation and / or stimulation engine system comprises any one or more of the features described in this disclosure.

[0022] In some embodiments, the pulse generation and / or stimulation engine method comprises any one or more of the features described in this disclosure.

[0023] Conventional stimulation systems may utilize capacitors to ensure or facilitate fail-safe operation because they are highly reliable and low cost.

[0024] Some systems cannot use capacitors because they are fully integrated on silicon, the output frequency is too low, the capacitors are too large, or some systems must pass direct current (DC). Some embodiments of the system can operate by providing a low frequency AC (LF-AC) waveform along with a low level DC bias with the goal of keeping the electrode operating range within a voltage window. The safety mechanism essentially ensures that both components stay within specifications and that the resulting electrode voltage stays within a predetermined range, evaluated, for example, by at least two independent check mechanisms. As with conventional high frequency AC capacitors, the capacitor can be switched in-line to protect against DC, and protection against switch failure can be provided by ensuring that DC does not substantially pass through the can, which is the only single failure path that DC can take.

[0025] Disclosed herein in some embodiments are alternatives to capacitors to enhance patient safety and / or use of capacitors in conjunction, possibly only for high frequencies, to provide protection.

[0026] Without being limited by theory, propagation of an action potential in electrically excitable tissue, such as neural tissue, results in a refractory period for sodium channels that is on the order of milliseconds, typically between about 1 and about 20 milliseconds, or between about 2 and 5 milliseconds when absolute and relative refractory periods are combined; therefore, very low frequency AC current waveforms having half periods significantly longer than this refractory period (e.g., greater than about 1, 1.5, 2, 2.5, 3, 10, 30, 50, 100, 300, 500, 1000, 2000, 5000, 6000 or more milliseconds) and with sufficiently low derivative rates (e.g., rise and fall times) so as not to elicit action potentials can also be used to create blocking or damping of tissue and be perceived as a direct current stimulus by electrically excitable tissue. Thus, direct current (DC) as defined herein includes low frequency AC current waveforms that are perceived as direct current from the perspective of the tissue in which action potentials or neural processing are being modulated and are functionally direct current. Indeed, the terms DC, DC waveform, low frequency AC, extremely low frequency AC, ULF, ULF waveform, etc. as used herein may all refer to the same signal, such as any signal or waveform that is perceived as a DC signal by tissue during at least a portion of the signal or waveform period. The frequency of such waveforms can be, for example, less than about 20 Hz, less than 10 Hz, less than 9 Hz, less than 8 Hz, less than 7 Hz, less than 6 Hz, less than 5 Hz, less than 4 Hz, less than 3 Hz, less than 2 Hz, less than 1 Hz, less than 0.5 Hz, less than 0.1 Hz, less than 0.05 Hz, less than 0.01 Hz, less than 0.005 Hz, less than 0.0001 Hz, or a range including any two of the above values, so long as the direction of current flow is constant over at least the entire refractory period of the target tissue, or at least twice, or at least five times, or at least ten times the time constant of the membrane channel responsible for the refractory period (e.g., the fast sodium channel inactivation gating time constant).

[0027] In some embodiments, the systems and methods can incorporate a variety of waveform frequencies, including high frequencies, e.g., about 1.2-50 kHz or higher, conventional frequencies, e.g., about 20-1.2 kHz, low frequencies, e.g., about 2-20 Hz, and very low frequencies, e.g., less than about 2 Hz. As noted elsewhere herein, direct current as defined herein includes low frequency AC current waveforms that are perceived as direct current from the perspective of the tissue in which the action potential is being modulated and are functionally direct current.

[0028] Chronic pain is a significant burden for individuals and society at large. In the United States alone, it is estimated that nearly 50 million adults have significant chronic or severe pain. (See Nahin, Estimates of Pain Prevalence and Severity in Adults: United States, 2012, The Journal of Pain, August 16, 2015 (8):769-780.) Worldwide, chronic pain is estimated to adversely affect over 1.5 billion people. (Borsook, A Future Without Chronic Pain: Neuroscience and Clinical Research, Cerebrum, June 2012.) Surgical techniques are sometimes applied to eliminate specific pain sources, but in many cases the exact cause of pain, often due to nerve impingement, is unknown and cannot be reliably addressed by surgical procedures. Alternatively, pain management can be addressed by overwhelming the central nervous system with stimulation signals that prevent the registration of pain inputs (gate control theory of pain). Typically, this stimulation is performed using metal electrodes and alternating current (AC) stimulation to generate these additional stimulation signals, in the case of spinal cord stimulation (SCS), to prevent the sensation of pain. However, one major drawback is the presence of paresthesia, a tingling sensation in the innervation area downstream of the stimulated nerve. Methods to eliminate paresthesia, which may be uncomfortable for patients, have led to stimulation means different from traditional tonic SCS (approximately 30-120 Hz), including high frequency stimulation (approximately 10 kHz) and burst stimulation (e.g., five pulses at 500 Hz delivered 40 times per second). (Tjepkema-Cloostermans et al, Effect of Burst Evaluated in Patients Familiar With Spinal Cord Stimulation, Neuromodulation, July 19, 2016 (5): 492-497.)

[0029] An alternative means of managing pain signal transmission to the central nervous system is to prevent the conduction of pain signals from peripheral sources by directly blocking or attenuating the pain signal, compared to masking the pain signal by generating alternative neural inputs to shut out and inhibit pain signal transmission as in traditional SCS and gating theory. One means of doing this is by applying direct current (DC) to the nerve to prevent the generation and transmission of action potentials (APIs). Since this does not stimulate the nerve as in traditional stimulation, paresthesia can be avoided. The mechanism leading to AP block is due to depolarization or hyperpolarization block, which inactivates sodium channels necessary for action potential events under the electrode site. (See Bhadra and Kilgore, Direct Current Electrical Conduction Block of Peripheral Nerve, IEEE Transactions on Neural Systems and Rehabilitation Engineering, September 12, 2004(3):313-324.) Wide dynamic range (WDR) neurons integrate pain signals and are also implicated as a contributing source of pain in patients, and application of direct current (DC) may be suitable to reduce this activity and affect the associated inhibitory and excitatory neurons that drive WDR activity.

[0030] Unrestricted use of direct current has long been known to be dangerous to nerve tissue due to the creation of toxic species at the electrode-nerve interface. Thus, systems and methods that facilitate safe delivery of direct current therapy are highly desirable. In some embodiments, the systems and methods can be configured to treat nociceptive pain. In some embodiments, the systems and methods for treating pain and other medical conditions can involve selective inhibition of anterior lateral column tissue in the spinal cord. Additionally, some embodiments relate to systems and methods for treating pain by the aforementioned systems and methods, specifically through selective inhibition of dorsal root tissue and / or dorsal root ganglion. Additionally, in some embodiments, disclosed herein are systems and methods for treating pain, specifically through inhibition or attenuation of one or more peripheral nerves.

[0031] In some embodiments, the systems and methods can safely block or attenuate pain signals within the spinal cord (including modulating pain processing) by delivering extremely low frequency stimulation to the epidural space for up to two weeks or more to achieve clinically measurable pain relief in patients with chronic low back pain who are candidates for spinal cord stimulation (SCS).

[0032] Targeted nerve blocks can be used to manage pain from specific dermatomes and pain at localized body sites. Several local targets involved in alleviating pain signaling can be addressed. For example, both the spinothalamic tract and more centrally located nerve tissues such as the dorsal root ganglion can be targeted to manage low back pain, sciatica, and complex regional pain syndrome (CPRS), among other pain considerations.

[0033] In some embodiments, the electrodes can include contacts that include a high charge capacity material. The electrode contacts can optionally be about 1 mm 2 and about 10 mm 2 Between or about 1 mm 2 , 2mm 2 , 3mm 2、4mm 2 、5mm 2 、6mm 2 、7mm 2 、8mm 2 、9mm 2 、10mm 2 、20mm 2 、50mm 2 、100mm 2, or a range including any two of the foregoing values. The electrode contacts themselves can be made of a high charge capacity material, such as those described in U.S. Patent No. 10,071,241 to Bhadra et al., which is incorporated herein by reference in its entirety. Alternatively, the electrode contacts can comprise a base that is at least partially or entirely coated with a high charge capacity material. In some embodiments, the electrode contacts can have a Q value of at least about 25 μC, 50 μC, 100 μC, 200 μC, 300 μC, 400 μC, 500 μC, 1000 μC, 2500 μC, 5000 μC, 10000 μC, 50000 μC, 100000 μC, 500000 μC, or more, or a Q value in a range including any two of the foregoing values. The Q value of an electrode contact can refer to the total amount of charge that can be delivered through the electrode contact before it begins to generate irreversible chemical reactions at a rate that cannot be removed by the body's nominal transport mechanisms. These chemical reactions include, but are not limited to, the generation of oxygen or hydrogen, or the dissolution of the electrode material. Non-limiting examples of high charge capacity materials are platinum black, iridium oxide, titanium nitride, tantalum, silver chloride, poly(ethylenedioxythiophene), and suitable combinations thereof. The electrode can comprise a fractal coating or high surface area format in some embodiments. The high charge capacity material can be configured to be monolithic or as a coating on a base substrate. Non-limiting examples of substrates for coatings include stainless steels such as 304 and 316LVM, nickel-cobalt-chromium alloys such as MP35N®, platinum and platinum-iridium, titanium, nickel-titanium alloys such as Nitinol. In some embodiments, the electrode can comprise tantalum coated with titanium nitride. Tantalum, as one non-limiting example, can be a particularly advantageous material due to its excellent radiopacity, thus allowing for improved implantation, verification, and / or removal of implantable neuromodulation devices. In some embodiments, the electrodes can include one or more of titanium nitride, tantalum, and MP35N.To create more surface area for electrochemical reactions to occur, conventional electrodes can be made with high surface area to volume structures, such as roughened surfaces, woven surfaces, patterned surfaces, reticulated foam structures, porous sintered bead structures, nano- or micro-patterned structures, to expose additional material surface area. In some embodiments, the electrode can be a SINE (separate interface nerve electrode) or EICCC (electron-ionic current conversion cell) electrode, in which the electrode is immersed in an electrolyte solution in contact at an ionically conductive material-electrolyte solution interface with an ionically conductive material in electrical contact with the cardiac tissue or an area proximate to the cardiac tissue, as described, for example, in U.S. Pat. No. 9,008,800 to Ackermann et al. and U.S. Publication No. 2018 / 0280691 to Ackermann et al., which are incorporated herein by reference in their entireties.

[0034] In some embodiments, disclosed herein are systems and methods for safely and effectively stimulating neural tissue that can advantageously utilize a variety of waveforms ranging from DC to high frequency. Although potentially very useful, stimulation with DC has not been commercially utilized for neuromodulation because neurostimulation systems capable of safely delivering DC for extended periods of time have not been available. Available commercial systems rely on charge balancing mechanisms to prevent DC delivery to limit irreversible electrochemical reactions. These systems can include blocking the DC component with a capacitor, a blocking capacitor, or a mechanism to remove charge buildup at the end of a stimulation cycle. While reliable, typical capacitors limit charge to less than about 1 millicoulomb (mC) per phase and do not permit utilization of very low frequency signals at large charge amounts above this charge capacity. Other widely utilized techniques rely on active balancing current sources, but these require redundancy to be fault tolerant, typically do not purposely control electrode voltages, which is critical for some electrode technologies, and have not been shown to be advantageous for long-term high charge delivery. Active systems in combination with coatings can achieve charge densities of approximately 2 mC / cm. 2While these densities have been exploited in devices such as retinal implants to increase photons density up to 1000 kV, these densities are still insufficient to allow for the use of the very high charge per phase waveforms required by DC or extremely low frequency waveforms with sufficient power amplitude.

[0035] Some embodiments involve high surface area electrode coatings combined with a bias current, e.g., a DC bias, to keep the electrode voltage in the optimum range for the particular electrode material for long term operational durability. This approach reduces the ∼50 μC / cm used in conventional systems. 2 to, in some cases, for example, about or at least about 5000 μC / cm without causing damage to the electrode or electrically excitable tissue. 2 , 25000μC / cm 2 , 50000μC / cm 2 The charge per phase can be increased to and beyond. Systems and methods configured to allow for an intentional net bias current, e.g., DC bias, such as via a control system, can advantageously maintain the health of high charge capacity electrodes in some cases (by preventing or inhibiting corrosion, e.g., oxidation, or other damage to the electrode), as well as minimize or prevent the generation of undesirable reactions and species, such as OH-, H+, or oxygen free radicals that lead to tissue damage. In some embodiments, the charge per anodic and / or cathodic phase is, for example, about 3000 μC, 3500 μC, 4000 μC, 4500 μC, 5000 μC, 5500 μC, 6000 μC, or above or below, such as between about 4000 μC and about 5000 μC per layer, and ranges including any two of the foregoing values.

[0036] In some embodiments, the systems and methods for delivery of electrical current through implanted electrodes do not include a capacitor, such as a blocking capacitor, hi some embodiments, the systems and methods for delivery of electrical current through implanted electrodes do not include a resistor.

[0037] In some embodiments, the bias current is the current resulting from the sum of the currents simultaneously delivered to the electrode contacts or working electrodes proximate the target excitable or voltage sensitive tissue. In some embodiments, the bias current is equal in magnitude and opposite in polarity to the sum of the currents simultaneously delivered to the electrode contacts or working electrodes. In some embodiments, the currents simultaneously delivered to the electrode contacts or working electrodes can be adjusted to modulate the bias current.

[0038] In some embodiments, conventional AC systems, which may include AC-only systems, utilize capacitors on each / all outputs, e.g., electrodes, to prevent delivery of DC to the tissue. Conventional AC systems typically do not include bypass switches that can avoid the capacitors that may be required for direct current (e.g., including the very low frequencies mentioned above) waveform delivery.

[0039] In some embodiments, disclosed herein is a neuromodulation device configured to perform in multiple electrical modulation modes with a single architecture. The device can include, for example, a power source, a control unit, and / or one or multiple current generators (e.g., unipolar and / or bipolar) configured to be connected to at least one, two, three, four, or five or more working electrodes.

[0040] In some embodiments, the device can include at least one, two, or more indifferent electrodes configured to block direct current, at least one, two, or more indifferent electrode switches configured in electrical communication with the at least one, two, or more indifferent electrodes, and at least one, two, or more blocking capacitor switches in electrical communication to bypass the at least one, two, or more blocking capacitors.

[0041] The device can include a first stimulation mode in which the current generator is configured to deliver an alternating current to at least one working electrode, and a second stimulation mode in which the current generator is configured to deliver a direct current to at least one working electrode, and both return electrodes are absorbed via an indifferent electrode.

[0042] In some embodiments, in the first stimulation mode, the control unit configures a separate current generator through the second working electrode, causes at least one indifferent electrode switch to disable electrical communication between the current generator and the at least one indifferent electrode, and at least one blocking capacitor is active to block direct current.

[0043] In some embodiments, in the second stimulation mode, the two current generators are configured to pass an offset current, e.g., from 0 μA to 1000 μA or more, through the indifferent electrode switch toward the indifferent electrode, and the control unit causes the at least two blocking capacitors to disable electrical communication between the current generators at at least one blocking capacitor, thereby bypassing the at least two blocking capacitors.

[0044] In some embodiments, the device can be configured such that very low frequency, conventional frequency, and high frequency alternating current can be delivered from the current generator to any number of working electrodes, anodic or cathodic bias current can be delivered to any number of working electrodes, and the blocking capacitor switch is configured to bypass the blocking capacitor, which can be advantageous, for example, for the life of the electrodes.

[0045] In some embodiments, the application specific integrated circuit (ASIC) including some embodiments herein is configured for low power and versatile AC stimulation. Some embodiments can add DC, but it is not necessarily optimal for DC because DAC (digital-to-analog converter) resolution is relatively low, limiting the selectivity of DC bias / offset (DC offset can be as low as 1 μA, for example, while providing high stimulation current, for example, up to 25 mA in the same channel), and the power while operating in DC mode is relatively high because it can be on continuously (100% duty cycle) or substantially continuously, whereas conventional AC stimulation pulses are 250 microseconds (1% duty cycle) every 25 milliseconds.

[0046] In some embodiments, referring to FIG. 1, a DC and AC approach using an application specific integrated circuit (ASIC) can include a bypass switch around each output blocking capacitor so that current, e.g., DC, can be delivered when the bypass switch is closed and charge balanced AC can be delivered when the bypass switch is open. This can be applied to each channel, e.g., channels 1 and 16. Thus, if the bypass switch fails and current flows due to an imbalance in the current sources to the tissue due to a shorted switch (or other cause), a "sensing" safety mechanism (the "sensing" circuit shown in FIG. 1) can be used to detect excess current flowing back through the system through an indifferent electrode, e.g., the IPG can, and shut off stimulation and / or take another safe operating measure.

[0047] In some embodiments, referring to FIG. 2, the DC and AC separate approach can be implemented with fewer components. For example, the blocking capacitors and bypass switches can be reduced to a single set between the source and a multiplexer (mux) that directs the current to several channels, such as one of the 16 channels. In some embodiments, two or more sets are used. In some embodiments, more or less than 16 channels can be used and / or the current can be directed to one or more channels. A second source and mux can also be used to sink or source current for bipolar operation. This separate approach can be advantageously simplified by not including a capacitor and switch for each mux output (electrode), which can reduce size, cost, manufacturing complexity, etc. If the separate approach described above and shown in FIGS. 3-4 is not implemented, a capacitor and switch for each channel may be required (e.g., 16 capacitor and switch pairs for a 16 channel system may be required). Similarly, in the DC and AC separate approaches, a "sensing" safety mechanism and an IE (indifferent electrode, or device housing or "can") can be used, as described with reference to FIG.

[0048] Figure 3 shows a schematic of an embodiment utilizing an ASIC linear current generator (e.g., Howland current pump) adapted to deliver both DC and AC. The DAC can directly control the current generator (source and sink) and an external capacitor bypass switch is included in the system to support DC. The bypass switch, e.g., a silicon bypass switch, is exposed to the body so that it can be shut down to ensure safety if any DC current is detected through the indifferent electrode (IE) / can.

[0049] Alternatively, both the AC and DC systems can be implemented in separate systems sharing common components. Some embodiments include a single bipolar channel that can be configured across any pair of electrodes in the system, such as potentially 16 electrodes. The AC system can be configured to include only a single current sink, and in some embodiments can be configured fast enough to generate pulses of about 10 microseconds, requiring a slew rate of about 10V / microsecond. This current source can be first routed through a cross-point switch to alternate polarity across a set of capacitors, and then routed through a multi-channel multiplexer, such as a 1-16 channel multiplexer. A single set of capacitors can be used, rather than a capacitor on each electrode, since safety can again be verified by detecting DC current through the IE / can.

[0050] For example, the AC discrete architecture embodiment described above can be extended to handle DC by adding a current source as shown diagrammatically in FIG. 4. To save power, the current source can be very slow, requiring, for example, about 5, 4, 3, 2, or 1 V / ms or less, rather than a higher amount, such as 10V microseconds or more, as required by the current sink. In addition, a switch can be added to bypass a capacitor that may not be present in the DC configuration. DC generally requires a higher current resolution than AC so that the bias / offset current can be set accurately. Thus, in some embodiments, the DAC resolution in both the current source and the current sink should be less than about 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 μA, or in some cases less than about 5 μA.

[0051] With regard to current sinks and current sources, in some cases a separate current sink may be simple and inexpensive to implement. Current sources may in some cases be more complex and may require circuitry similar to that shown in Figures 5A-5B. Current sinks implement AC and generally require high performance, whereas current sources generally only handle slow DC and can operate at much slower speeds, advantageously reducing power significantly.

[0052] As described herein, some stimulation systems utilize capacitors to ensure near fail-safe operation because they are passive, low-cost, and generally reliable components. However, some systems are fully integrated on silicon and therefore cannot (or at least are less desirable to) use capacitors because the output frequency may be too low, the system may be able to pass DC, and / or the capacitors are too large.

[0053] FIG. 5B is a schematic diagram of a bipolar current generator that can be dynamically reconfigured to generate AC or DC stimulation (also referred to as operating in AC or DC mode). DAC A and DAC B provide the stimulation amplitude. For slow-moving DC stimulation, DAC A and DAC B are updated slowly (e.g., at 100 Hz or less) with a bias added to each current. For AC stimulation, DAC A and DAC B are updated with the values ​​of the activation and recovery currents, and S1 is switched to form fast AC activation and recovery pulses. A discharge switch is available. A discharge switch is available to create other AC modes, such as passive recharging.

[0054] FIG. 6 illustrates a schematic block diagram of a fail-safe hybrid system. The system may have a first control unit, e.g., a main microcontroller unit (MCU) configured to implement a charge management algorithm through a current generator and an IE voltage output. The system may also include a second MCU, e.g., a watchdog MCU, also referred to herein as a supervisory MCU, that may have an independent charge management algorithm that may monitor the main MCU and shut down the system in case of a mismatch. The main MCU and watchdog MCU may be configured to monitor the electrodes and the system in a variety of ways that may include, for example, any number of: (1) monitoring electrode voltage to protect against electrode degradation and failure and electronic failure; (2) IC power monitoring to protect against device failure in AC or DC modes; and / or (3) voltage waveform morphology analysis to protect against device failure. During AC mode, blocking capacitors may be switched in-line. The main MCU and watchdog MCU may cross-check each other for proper orientation. The system may include a third MCU, e.g., a supervisory watchdog MCU, that may prevent the device from being reset. In external, non-implantable versions, only the clinician may be allowed to replace the battery to avoid terminating the stimulation cycle when the electrodes are loaded with charge.

[0055] FIG. 7 shows a table of non-limiting potential failure mechanisms listed in rows and mitigation mechanisms listed in columns. According to some embodiments, a checkmark indicates which mitigation protects against which failure. If a failure occurs, stimulation is stopped immediately (instant off) or at the end of the stimulation cycle if it is beneficial to terminate in a charge balance state. For example, bias current monitor out of range results in instant off stimulation to protect against surface electrode (IE) disconnection, current source error, coupling capacitor error, or instrumentation signal chain error. Periodic VPP out of range (e.g., 10 or other number of cycles) is the primary mechanism to protect against long-term electrode degradation, resulting in stimulation terminating at the completion of the stimulation cycle. Waveform morphology violations (e.g., 10 or other number of cycles) result in the stimulation cycle being terminated and completion of the stimulation cycle to protect against electrode disconnection, current source failure, or instrumentation error. MCU / WD voltage monitoring protects against problems with stimulation or other power supply circuits, immediately terminating stimulation and possibly turning off the power. Hardware watchdog protection results in a general reset and immediately terminates the stimulation cycle to protect against firmware / MCU failures. Offline impedance check - pre-check to rule out faulty electrodes and insufficient electrode capacitance. MCU / WD cross-check results in a general reset and immediately terminates the stimulation cycle to ensure both MCUs are operating properly. Independent charge management algorithms (two different algorithms with independent code bases) result in a general reset and immediately terminates the stimulation cycle to protect against firmware bugs and unexpected algorithmic flaws.

[0056] In some embodiments, the device can include a virtual ground configured to be operably connected to the indifferent electrode, the virtual ground being capable of being set to any level to minimize power dissipation.

[0057] In some embodiments, the current drawn from the output multiplexer is measured to detect any faults in active silicon components that are directly connected to the body, particularly to prevent unintended DC current due to component failure caused by ESD discharge damage.

[0058] In some embodiments, the device includes any number of the following mitigation mechanisms: (a) indifferent electrode power monitoring stops operation if the bias current deviates from a preset minimum and maximum range, and the current used can be processed by statistical processing to remove noise; (b) electrode voltage monitoring, either from each working electrode to the indifferent electrode, each working electrode to the reference electrode, or between a pair of working electrodes; (c) electrode monitoring is resolved instantaneously or statistically resolved over a preset time, e.g., from 1 microsecond to 1 hour or more or less, or is synchronized to waveform transitions, and statistics can include mean, median, variance, minimum, and / or maximum; (d) electrode monitoring can examine electrode voltages in their entirety or can be broken down into components using a filter mechanism or by subtracting components based on what is known about the electrode, e.g., what was measured, or the electrode specifications. As an example, the aforementioned filtered voltage-stimulation current * measured access resistance can be below a specified value.

[0059] Figure 8 shows a graph of lost capacity that may be related to voltage protection. Cyclic VPP: VPP-2*RA*I, which can help ensure that the peak voltage over a stimulation cycle remains within predefined limits to ensure that the electrodes have sufficient capacity over time. Electrode waveform morphology (sawtooth) can help ensure that the electrode voltage waveform is as expected for a given current, which can help ensure that the system is operating properly.

[0060] 9A and 9B relate to bias current monitoring. FIG. 9A shows a graph for a broken reference electrode. FIG. 9B shows a graph for the bias current being removed. Bias current monitoring can protect against a variety of failures that can include IE failure (open circuit or Hi-Z), WE failure (open circuit or Hi-Z), WE current source failure (high or low), IE voltage source failure (no current driving the current source to failure), and / or capacitor bypass switch failure (current leakage or fail open). For DC-specific modulation modes, the monitor can check that the bias is in the correct range (e.g., 25-75 μA). For AC-specific modulation modes, the monitor can check that the DC current is below a predetermined value, such as, for example, ≦100 nA (e.g., electronic or multiple capacitor failure).

[0061] FIG. 10 relates to reducing (e.g., minimizing) irrecoverable charge. FIG. 10 shows stimulation onset versus time in seconds. Injection of bias current can place the electrode in an operating voltage range that can allow charge and / or electrode life to be maximized, etc., increased. The operating condition of the electrode can be determined, which can include determining that the electrode is in good operating condition. For example, the electrode can be determined to be in good operating condition by (1) determining (e.g., ensuring) that the peak of the reference voltage waveform is below a calculated or empirically calculated voltage, and / or (2) integrating the voltage of the cycle as an indicator of irreversible charge and / or determining (e.g., ensuring) that it is below a certain threshold.

[0062] FIG. 11 shows an example block diagram for HW and FW failsafe. Charge management algorithm - main MCU controls the ASIC (or discrete current generator). MCU / WD voltage / current monitoring - independent ADCs and algorithms in main and watchdog can be kept alive by the watchdog MCU ensuring HW and FW are operational. MCU / WD cross-check - main and watchdog MCUs check each other to ensure HW and FW are operational. MCU / WD ASIC reset - if a problem is detected, either the main MCU or the watchdog MCU can reset the ASIC.

[0063] A block diagram of an exemplary stimulation engine (sometimes referred to as a waveform generator or therapy waveform generator) capable of providing DC and AC therapy, including stimulation with a single architecture, is shown in FIG. 12. A conventional approach for medical devices is to utilize only one microprocessor to both control the generation of stimulation on the electrodes and to check the stimulation on the electrodes. Such an approach makes the therapy system susceptible to a double failure that can result in patient harm. From a safety perspective, this results in all system software having a higher risk classification (e.g., higher risk class C instead of lower risk class A or B). By providing a separate microprocessor that monitors the electrodes, as shown in the architecture of FIG. 12, three simultaneous failures need to occur to result in a harmful situation for the patient. A separate safety microprocessor (e.g., the safety MCU shown in FIG. 12) reduces the overall risk and improves safety. This allows the safety classification of the software and system to be reduced (from higher risk class C to the lowest risk class A). This also greatly simplifies the design and testing of the system. The stimulation engine can stimulate with a single bipolar pair of current generators. The main microcontroller unit (MCU, processor, or controller) can generate the stimulus waveforms, and the safety MCU can continuously verify proper system operation. A boost converter and LDO (low dropout regulator) can set a low noise stimulus compliance voltage (VSTIM) to drive the bipolar current generators SRCA, SRCB. The current generators SRCA, SRCB can be fast enough to support AC waveforms with rise and fall times of 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 microseconds. The drive voltage (VSTIM) for such generators is high enough so that the current generators operate within the common mode input range to conserve power.

[0064] During low duty cycle AC (e.g., tonic) stimulation, VSTIM can be set to substantially (e.g., almost) zero volts, shutting down the stimulation engine to conserve power. Since the system can operate with a single power supply, the virtual ground (VIE) can be set to the mid-rail for AC. During DC (e.g., ULF), VIE can be set to a fraction of VSTIM depending on the bias voltage created by the bias current, which occurs near the electrode operating voltage to conserve power. The stimulation voltage and current can be floated around VIE. Since the bias current moves the voltage below the mid-rail, VIE can be designed to track those voltages to conserve power. For DC mode, VIE can absorb a constant offset current and can be connected to an indifferent electrode (IE), which can be a surface electrode for the stimulation engine and a can (e.g., a housing or enclosure) for the stimulation engine. During AC mode, charge imbalance that may collect inside the blocking capacitors CBA, CBB due to charge imbalance can be discharged to VIE. In AC mode, the indifferent electrode IE is disconnected from the patient. The VIE can be set to either the VSTIM or ground rail when the electrode reaches the bias voltage to further optimize power.

[0065] The bipolar current generators SRCA, SRCB can push or pull current to support the required balanced or intentionally unbalanced bipolar stimulation modes. For example, the generators SRCA, SRCB can operate in bipolar mode and can be configured to deliver opposite equal or unequal currents. In AC mode, they can be configured to generate equal and opposite currents. In DC mode, they can be opposite and can optionally include slightly offset currents. Since the matching requirements are very high (approximately 1 μA), separate trim DACs (digital-to-analog converters) (TRIMA DAC, TRIMB DAC) for both currents are used. Both DC offset and AC zero adjustment can be achieved by utilizing trim DACs, e.g., TRIMA DAC, TRIMB DAC. For example, due to mismatch between the complementary pair of current generators, there may be residual nonlinearity after calibration. To address this, one of the current generators (e.g., SRCA) can be optionally selected as a reference source. A secondary calibration can be performed to force the adaptive current generator (e.g., SRCB) to match the reference source (e.g., SRCA). This calibration is applied to the TRIM DAC (e.g., TRIMB DAC) on the adaptive current generator (e.g., SRCB) and then matches the differential nonlinearity, allowing the normal calibration to correct the global nonlinearity (including the differential nonlinearity). In DC mode, the source DACs SRCA DAC, SRCB DAC can deliver a slowly changing current, and the trim DAC can trim the value and set the offset as described herein. The source DACs SRCA DAC, SRCB DAC can be updated by software via the SPI port when the current value needs to be changed, but can be changed at up to 100Hz or faster, or any other rate, but during the stimulation plateau, a single stimulation value can last for several seconds.

[0066] In AC mode, the stimulus can be changed rapidly so that the cathode (activation) current amplitude can be programmed into one source DAC, e.g., the SRCA DAC, and the recovery amplitude can be programmed into the other source DAC, e.g., the SRCB DAC, before the stimulus begins or when the stimulus is changed. AC pulses can be formed quickly and efficiently by flipping the source of each current source to be either one source DAC, e.g., the SRCA DAC, a mid-supply (e.g., for zero current), or the other source DAC, e.g., the SRCB DAC.

[0067] Two blocking capacitors CBA, CBB can be used to ensure DC blocking in AC mode, but can be bypassed in DC mode. Rebalance switches RBSWA, RBSWB (also referred to as DSW1, DSW2, REBALA, REBALB, D1, D2) can recover charge from blocking capacitors CBA, CBB and can be used for self-test and other calibration modes. Discharge switches RBSWA, RBSWB can be used to discharge blocking capacitors CBA, CBB. In one embodiment, the stimulation engine includes one or more switches, e.g., ULFSW, which can be closed to bypass / shorten blocking capacitors CBA, CBB when operating in DC (or ULF) mode, but can be opened to pass drive current through blocking capacitors CBA, CBB when operating in AC mode. The drive current is then directed through multiplexers SRCA MUX, SRCB MUX and routed to the desired electrodes E01-E16. During AC mode, capacitors CBA, CBB can be used to ensure that the current to electrodes E01-E16 is balanced.

[0068] In one embodiment, the blocking capacitors CBA, CBB are placed at the input side of the multiplexers SRCA MUX, SRCB MUX. Such an arrangement eliminates the need to place separate capacitors on each electrode E01-E16, which simplifies the circuit design and reduces the footprint of the implantable stimulation engine. The multiplexers SRCA MUX, SRCB MUX advantageously allow for significant customizability of the stimulation engine. For example, the implantable lead of the stimulation engine may include 16 electrodes. The multiplexers SRCA MUX, SRCB MUX allow the stimulation engine to be configured to deliver any desired electrical waveform to any desired electrode. Furthermore, the multiplexers SRCA MUX, SRCB MUX or other multiplexers, such as VRE, allow any of the electrodes to be selected to function as a reference electrode. With such configurability, the can or indifferent electrode of the stimulation engine does not necessarily have to be utilized as the reference electrode of the stimulation engine. Instead, any one of the electrodes E01-E16 may be utilized as the reference electrode. Additionally, each electrode can be selected by multiplexers VRE, SRCA MUX, SRCB MUX to act as either an anode or a cathode of the stimulation engine's tissue stimulation signal.

[0069] Also during AC mode, the IE can be disconnected through a fault-tolerant set of series IE switches IESW1, IESW2. The IE current sensor Iie can be used for fault detection and to measure a constant offset current in DC and can also be used for self-test calibration and diagnostic modes. Current steering diodes (not shown) can protect all system outputs from overvoltage at the terminals and the series configuration can protect against single point faults and shorts to ground.

[0070] Electrocautery can present significant challenges to therapeutic waveform generators, including SCS devices, as they can provide 200W@1000V@490kHz of power. Defibrillators present similar challenges. These voltages can result in damage to the driving electronics, resulting in device malfunction and failure. This challenge is amplified in devices with spaced apart electrodes, such as those with spaced apart working and indifferent or return electrodes. The indifferent and working electrodes can be separated by large distances, resulting in a high potential difference between the electrodes that is provided to the electronics. One example of such a configuration utilizes an active can, where the metal casing is an active component in the electrical circuit, and the can is not located near the working electrode. Another example includes configurations with an inactive can, where the can is not an active component in the electrical circuit, and an alternative indifferent or return electrode, including but not limited to a surface electrode, a separate embedded electrode, or an electrode contact on an electrode array, where the indifferent or return electrode is not near the working electrode. Other examples include configurations with locally located indifferent or return electrodes, including, but not limited to, configurations where electrode contacts on the array are designated as return or indifferent electrodes. In all of these non-limiting examples, spacing between working electrodes typically presents less risk due to the relatively reduced separation distance to the indifferent or return electrodes. However, these working electrodes present a non-zero risk of electrocautery injury.

[0071] It is therefore desirable to include a protection mechanism to protect against electrocautery, defibrillator, or other high voltage / high current damage. Some therapeutic waveform generators and SCS systems utilize capacitors at the electrodes to provide protection from electrocautery damage. However, the necessary lack of isolation capacitors at the electrodes in low frequency, very low frequency, and DC systems necessitates an alternative approach that does not rely on capacitors.

[0072] FIG. 13 shows an example of a system for protecting against high voltages and / or currents utilizing current steering diodes and fast acting positive temperature coefficient (PTC) devices. A Zener diode in series with two PTCs connects the electrode can to the drive electronics. In the presence of a moderate magnitude externally applied voltage, such as an electrostatic discharge, the Zener diodes clamp the external voltage to a safe level, such as 5V, 10V, 15V, 20V, 25V, less than 25V, or less than 30V. The externally applied voltage resulting from electrocautery presents a high voltage that results in irreversible destruction of the Zener diode. Placing one or more PTC devices in series with the Zener diodes protects the Zener diodes from damage such as disconnecting the electrode can from the drive circuit. The high voltage / current results in a temperature increase across the PTC, an increase in the PTC resistance, and a significant reduction in the power burden of the Zener. FIG. 14 shows how this series configuration allows for voltage clamping to approximately 18V in the presence of a high voltage electrocautery signal.

[0073] Referring again to FIG. 12, the stimulation engine instrumentation can include measurements of working electrode voltages VweA, VweB, an indifferent electrode voltage Vie, and a reference electrode voltage Vre, where the reference electrode is one of a total number of selectable working electrodes, e.g., 4, 16, etc. All of the above instrumentation can be used for diagnostics, calibration, and / or to implement safety and control measures. All voltages can be buffered before routing to both the main MCU ADC and the safety MCU ADC, and these separate MCUs can be used at least in part to achieve a safe, fault-tolerant system.

[0074] Four (or more or less) of the 16 (or more or less) working electrodes (e.g., E01, E08, E09, E16) can be wired to a reference electrode multiplexer VRE. One (or more or less) of those electrodes can be electronically selected as the reference and can be in electrical communication with a VREF amplifier (not shown) via two series resistors VR1, VR2 to limit the current to 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 μA in case of worst case amplifier failure. The reference electrode multiplexer VRE can be momentarily selected when sampling the reference voltage. Measurement of the effective reference voltage Vre can be made by any electrode that is not being used to stimulate or otherwise provide a therapeutic signal to the patient.

[0075] AC neurostimulation systems may rely primarily on isolating the active circuitry from the body using a series capacitor. In conjunction with an internal discharge resistor / switch, the capacitor not only protects against circuit failure but also provides a charge balanced waveform. Large capacity electrode systems utilizing balanced or unbalanced charge biphasic waveforms operating at very low frequencies utilize DC stimulation and cannot easily utilize capacitors. As a result, alternative safety mechanisms must be implemented. Similarly, the same limitations may also apply to systems utilizing balanced charge biphasic waveforms (e.g., ULE waveforms in balanced systems). Therefore, alternative (non-capacitor-based) solutions may also be utilized in such systems.

[0076] In one embodiment, the DC mode operates by providing an extremely low frequency unbalanced waveform that allows the electrodes to operate within a protected voltage region where long term electrode capacitance is optimized and preserved. Safety mechanisms can ensure that the resulting electrode voltages remain within a predetermined range as assessed by at least two independent mechanisms, and in the event of one or more system failures, any detected failure can result in a stimulation shutdown and power down of the stimulation engine.

[0077] To better understand such safety mechanisms, the electrode can be modeled by a simplified Randles cell, i.e., a series access resistance (Ra), and a capacitance (Cdl), and a polarization resistance (Rp or Rct). Since the polarization resistance is about 10 times greater than Ra, Ra is ignored in this procedure. The total voltage across the electrode (Vt) is equal to Ra*I+cyclic Vpp, where cyclic Vpp is the peak-to-peak voltage across the capacitance component (Cdl) of the electrode. Given this relationship, Va (from Ra×I) and cyclic Vpp can be separated in each stimulation cycle using a real-time measurement of Vt, and Ra can be calculated.

[0078] To ensure tissue safety, it may be important to operate the electrode within its electrode capacity. Operating the electrode outside of its capacity may eventually reduce the electrode capacity and promote reactions that may affect tissue health and cause irreversible electrochemical reactions. The cyclic Vpp is the main measure of electrode health and is inversely proportional to the electrode capacity. Once the electrode achieves steady state operation, the cyclic Vpp is expected to be approximately constant. If changes occur to the electrode during its life, they can be detected via the cyclic Vpp and stimulation can be adjusted to ensure operation within the electrode capacity or the stimulation electrode can be changed as needed.

[0079] In AC stimulation mode, blocking capacitors CBA, CBB can be placed between the electrode contacts and the current output to protect against DC. In DC neuromodulation mode, e.g., stimulation mode, the capacitors CBA, CBB can be disabled using the switch ULFSW. Using the capacitors and switches, various failure modes can be realized. For example, if the capacitors CBA, CBB fail, there can be a failure mode in which DC can flow to the indifferent electrode IE and the DC current can be detected (e.g., by the current sensor Iie, etc.). If the capacitor fails, there can be a failure mode in which the other capacitor can protect the body from DC through the other electrode. If the switch fails, there can be a failure mode in which DC can flow to the indifferent electrode that can be detected. If the current output in AC mode fails, there can be a failure mode in which the capacitor can protect the body from DC. If the current output in DC mode fails, there can be a failure mode in which the capacitor can protect the body from DC.

[0080] The Stimulus Engine may include two processors: a Main MCU and a Watchdog or Safety MCU. In DC mode, the Main MCU implements a Charge Management Algorithm (CMA) using a current generator and an IE voltage output (virtual ground). The Watchdog or Safety MCU may have an independent charge management algorithm that monitors the Main MCU and can shut down the system in case of a mismatch. The Main MCU and Safety MCU may monitor each other with independent ADC monitors, may monitor electrode voltage to protect against electrode degradation and failure and electronic failure, may monitor IE current to protect at proper DC levels against device failure, and / or may monitor voltage waveform morphology to protect against device failure. The Main MCU and Safety MCU may cross-check each other for proper operation. Both the Main MCU and Safety MCU may reset / disable the ASIC. There may be various failure modes. For example, if the charge management algorithm fails in the main MCU, the main MCU may observe an electrode voltage problem, the main MCU may determine if the IE current has gone out of range, the safety MCU may monitor for an electrode voltage problem, and / or the safety MCU may determine if the IE current has gone out of range. If the main MCU malfunctions, the safety MCU may observe such a situation and request a stimulation stop and then reset the main MCU and the ASIC, and / or the supervisor chip may monitor the condition and force a reset of both the main MCU and the safety MCU and the ASIC. If the safety MCU malfunctions, the main MCU may monitor the condition and request a stimulation stop and then reset the safety MCU and the ASIC, and / or the supervisor chip may monitor the condition and force a reset of both the main MCU and the safety MCU and the ASIC.

[0081] In addition, the main MCU can control the current generator (e.g., using the TRIMA DAC and SRCA DAC that control the current source SRCA, and the SRCB DAC & TRIMB DAC that control the current source SRCB) and the IE voltage output (virtual ground) (e.g., using the VIE DAC and amplifier DRV). The safety MCU can have an independent charge management algorithm that can monitor the main MCU and shut down the system in case of a mismatch. The main MCU and safety MCU can monitor each other and each can include independent ADC monitors, i.e., IE current to protect against device failure and improper DC levels. The main MCU and safety MCU can cross-check each other for proper operation. Both the main MCU and safety MCU can reset / disable the ASIC. There can be several failure modes that can include failure of the capacitor (e.g., CBA, CBB or capacitor bypass switch (e.g., ULFSW) can cause IE current to flow.

[0082] The stimulus engine (e.g., the stimulus engine of FIG. 12 or other stimulus engines described herein) may be implemented as an application specific integrated circuit (ASIC). Thus, the stimulus engine may also include three or more bypassable blocking capacitors, e.g., one blocking capacitor per electrode, e.g., 16 capacitors if 16 electrodes are used. The current output ASIC is clocked by an oscillator and may receive and execute commands from the main MCU, and / or the analog differential electrode voltage is buffered by an internal amplifier and then an external amplifier. Various failure modes may exist. If the current output ASIC current source, oscillator, and / or amplifier fail, the main MCU and safety MCU may detect an error in the IE current, and / or the main MCU and safety MCU may detect an error in the electrode voltage, including periodic Vpp, waveform morphology, and / or electrode voltage.

[0083] In one embodiment, the IE amplifier DRV in FIG. 14 can buffer the voltage generated from the VIE DAC command from the MCU to drive the indifferent electrode IE, sometimes called virtual ground. In DC mode, the IE can absorb bias current to protect the electrode. In AC mode, the IE current is typically not utilized. The current sensor Iie can measure the current to the IE to test various failure modes. For example, if the IE amplifier DRV fails, the current output may not accept additional current from the IE, causing the electrode voltage to be in error and may be recognized by the MCU. In DC mode, if the current sensor Iie fails out of range, the MCU can shut down the stimulation. During AC mode, the current sensor Iie can be tested periodically to avoid a double failure case when the AC current sensor Iie fails at a low level and the capacitor switch, e.g., ULFSW, fails.

[0084] The stimulation engine system disclosed herein may differ from other systems in various aspects. In one aspect, the system disclosed herein may use an ultra-low frequency (ULF) stimulation waveform and a low current offset ("current offset"), which may be in the form of a constant current offset. The ULF waveform current amplitude can be adjusted for individual patients to achieve efficacy. The low current offset can be used to bias the working electrode operating voltage such that the working electrode operating voltage operates at an increased (e.g., maximum) long-term charge transfer potential.

[0085] The ULF waveform can be charge-balanced (minus current offset) over the stimulation cycle, and is preferably stopped at the end of the cycle to avoid adverse patient perception as well as undesired unperceived neuromodulation. Similarly, in some cases, the ULF waveform has all smooth transitions (e.g., rounded edges rather than square waves) between waveform segments to minimize such adverse patient perception and undesired unperceived neuromodulation. In bipolar mode, a current offset can be introduced into the system by shifting each of the charge-balanced ULF waveforms by a predetermined percentage, e.g., 1 / 2 of the target current offset level, and the current offset, which is the unbalanced part of the waveform, can be removed via the indifferent electrode (IE).

[0086] A non-limiting exemplary measurement of a DC (e.g., ULF) waveform stimulating a DC lead ex vivo (generated by the stimulation engine during the DC mode of operation of the stimulation engine) is shown in FIG. 15. Bipolar current is generated by sourcing current from the SRCA, sinking current into the SRCB, and then switching polarity to source from the SRCB instead and sinking through the SRCA. Switching polarity at a specific rate allows for the generation of any of the frequencies or frequency ranges described herein with stimulation amplitudes of any of the stimulation amplitudes described herein. In one embodiment, the bias of each electrode is any bias value described herein and can be in the mA, μA, or nA range. The bias is generated by intentionally mismatching the source and sink currents between the current generators and can be set to a specific polarity without frequency. If the bias current is constant and negative, it can shift the magnitude of the positive values ​​of the extremely low frequency waveform. If the bias current is constant and positive, it can shift the magnitude of the negative values ​​of the extremely low frequency waveform. Using this technique, complex non-DC biases can also be introduced.

[0087] A non-limiting example of an AC waveform (e.g., generated by the stimulation engine during an AC mode of operation of the stimulation engine) is shown in FIG. 16. For clarity, only the Iwe2 and Vwe2-Vie voltages of the bipolar pairs SRCA, SRCB are shown. The amplitude of the waveform can be any amplitude described herein, 100 μA, 500 μA, 1000 μA, 2000 μA, 3000 μA, 4000 μA, 5000 μA, 6000 μA, 7000 μA, 8000 μA, 9000 μA, or 10000 μA, or any other amplitude, and the recovery pulse is a fraction of the amplitude, such as ½, ⅓, ¼, ⅕, ⅙ ... The recovery pulse may be 1x, 2x, 3x, 4x, 5x, 6x, 7x, 8x, 9x, 10x, or other multiples longer than the active pulse. The stimulation engine may drive zero current between the activation and recovery pulses. After the recovery pulse is completed, the current source maintains near zero current for the remainder of the pulse until a period corresponding to the pulse period is reached.

[0088] The stimulus engine can include several mitigation mechanisms, which can be categorized into firmware-based charge management algorithms (CMA) and hardware mitigation mechanisms, as summarized in the tables shown in Figures 7 and 17. Although many of the mitigation mechanisms are described with respect to systems that deliver ULF current with a bias current, the same mitigation mechanisms can be used for systems that deliver ULF current without a bias current as well.

[0089] The CMA components can be implemented independently on separate MCUs, e.g., a main MCU and a safety MCU. Two independent firmware images executing two independent algorithms running on two independent processors can have a very low probability of failing within a finite window of time.

[0090] The table in FIG. 17 lists several mitigation mechanisms or fault detection events. Each row in the table corresponds to a mitigation mechanism. The columns in the table correspond to a mitigation mechanism ID, a description of the mitigation mechanism, and a comment associated with the mitigation mechanism. Any number (e.g., all or a subset) of the mitigation elements disclosed herein can be included and / or excluded within the neuromodulation engine depending on the desired clinical outcome. Furthermore, any one of the mitigation mechanisms, when detected by the controller or processor, can trigger a system response including, but not limited to, preventing operation of the stimulation engine, removing the Vstim signal, disconnecting the battery, etc. Additionally, the mitigation mechanisms or fault conditions can be detected by the hardware, software, and / or firmware of the stimulation engine.

[0091] The stimulus engine may use various safety mechanisms to ensure proper functioning and redundancy checking of system performance. For example, the CMS mechanism involves providing two or more processors (e.g., a main MCU (M-MCU), a safety MCU (sometimes called a watchdog MCU or W-MCU)) that operate independently and monitor each other's performance, including the operation of the charge management algorithms (CMAs) of the other processors. The two processors may continue to operate upon the unlikely failure of one of the processors.

[0092] The IIE mechanism refers to providing current monitoring to detect current errors when operating in DC mode. The IIE current errors may result from either SRCA, SRCB, VIE faults, interconnection errors, or shorts to power or ground. For example, the stimulus engine of FIG. 12 may include a current sensor Iie, as described in more detail herein.

[0093] The HBSC mechanism refers to monitoring the MCU heartbeat signals and sequence checking. If either the main MCU or the safety MCU fails to generate a heartbeat signal or if the sequence contains an error, one or both MCUs are reset. The heartbeat signal indicates that the microprocessors (main MCU and safety MCU) are running. However, even if they are running, they can still become unsynchronized. The heartbeat count ensures that both processors run for a long time without undetected resets and provides an additional safety measure to ensure that they remain synchronized. Such a configuration can be used to detect unexpected independent MCU reset conditions (e.g., out of sync, etc.).

[0094] The VMIN monitor can indicate whether VSTIM (stimulation voltage) (e.g., as detected at selected working electrodes E01-E16) is at a desired level. The VMIN signal can indicate whether VSTIM exceeds the desired level, fails to achieve the desired level, or is outside a threshold difference from the desired level.

[0095] The VSTIM mechanism refers to the Vstim or stimulation voltage monitor. Vstim may be generated by a boost converter as shown in Figure 12. Vstim may be actively regulated and monitored to ensure that it does not exceed an expected maximum voltage. This protects against open circuits or degraded electrodes.

[0096] The VOSF monitor can indicate whether an overcurrent fault has occurred. For example, if the IVOS signal exceeds a threshold current level for more than a specified duration, a fault condition can be detected and a system response (such as that described herein) can occur. The IVOS signal can correspond to a monitored current signal from an output power supply circuit. The current of the power supply circuit to the multiplexer is monitored because a current that exceeds an expected value can indicate a multiplexer failure.

[0097] VOVP mechanism refers to the VSTIM overvoltage protection mechanism. This hardware mechanism shuts down the system to avoid damaging the circuitry and exposing the patient to undesirable voltage levels.

[0098] The VPP mechanism refers to monitoring the health of the electrodes and was described above with reference to FIG. 8. Other mechanisms for monitoring electrode health and performance may be provided as well. For example, real-time monitoring of electrode performance by determining the direct access resistance (Ra), capacitance (Cdl), and polarization resistance (Rp or Rct) of each electrode can indicate whether the electrodes are operating as expected. For example, changes in electrode structure, plating, and / or location within the subject may lead to changes in one or more of such electrode parameters. Real-time monitoring provides an indication when an undesirable change occurs such that system operation may be paused or an electrode may be identified as possibly failing. Faulty electrodes may then be removed from the output path of the stimulation engine by controlling a multiplexer to avoid selecting such electrodes for stimulation output.

[0099] Examples of real-time measurement and calculation of circuit parameters are shown in FIGS.

[0100] In some configurations, the series access resistance Ra and double layer capacitance Cdl can be measured using a test rectangular biphasic current pulse and a potential [Vwe-it(t)] measured between the working and indifferent electrodes. The rising and falling edges of the rectangular current waveform are the voltage step V at the potential measured as a result of the resistive drop across the solution resistance (Ra), ignoring the contribution from the electrode capacitance to the high-pass characteristics of the capacitive interface. step Thus, the voltage step produced by a current step of known magnitude I at the beginning and end of the biphasic pulse corresponds to Ra=V step / I gives Ra, and during polarity reversal Ra=abs(V step / (2*I)) gives Ra. The capacitance is determined by the approximately linear relationship between the accumulated charge across the electrode interface and the voltage, and is expressed as the time t from the rising edge to the falling edge of the constant current I. plateau Voltage increase of V plateau The voltage measurement can be determined from Cdl=I*t plateau / V plateau Cdl is applied from or to some portion of the plateau. In some configurations, the biphasic waveform can consist of a single biphasic pulse, or a series of biphasic pulses. In some configurations, the biphasic waveform can be applied prior to or at the cessation of delivery of the therapeutic waveform to establish initial and final values ​​of Ra and Cdl. In some configurations, the biphasic waveform can be applied periodically during pauses in the delivery of the therapeutic waveform. In some configurations, the biphasic waveform provides a very low current I and a short period followed by a small t to allow real-time assessment of electrode parameters. plateau and can be used to apply between periods of the therapeutic waveform without pausing the treatment (FIG. 18).

[0101] In some configurations, the series access resistance Ra and the cyclic peak-to-peak voltage Vpp are determined by the potential [V we-ie The pulse width is approximated using a set of sampled points from the pulse width [I(t)] and the instantaneous stimulation current [I(t)]. The sampled points are then analyzed using an algorithm to calculate Ra and Vpp. A similar analysis can be performed to calculate the pulse width [V we-re An example of such a configuration is shown in Figure 19.

[0102] In one configuration, the algorithm includes the following steps.

[0103] 1. Time point T2 is set at the current zero crossing point.

[0104] 2. A set of time points is bounded by time points T1 and T3, where T1=T2-δ T and T3 = T3 + δ T where δ T >0.

[0105] 3. V we-ie (t) is sampled at all time points bounded by T1 and T3.

[0106] 4. I(t) is sampled at all times bounded by T1 and T3 from the device command to the output or from the output current monitor.

[0107] 5. Access resistance R est The set of values ​​of R max ≧R n ≧R min Entry R n where R min is the minimum predicted R a is an approximation of R max is the maximum expected R a is an approximation of

[0108] 6. A set of voltages V(t) is est For each entry in, it is calculated as follows: a. V(t)={|V we-ie (t)-I(t)*r|:r∈R est , T1≦t≦T3}

[0109] 7. R est For each entry in, find the local maximum of each set of voltages.

[0110] 8. R a , the R that produces the smallest local maximum. est Set the elements of

[0111] 9. Vpp can be calculated by the following formula, where T4 is the previous zero crossing point: a. Vpp==|V we-ie (T2)-I(T2)*Ra|-|V we-ie (T4)-I(T4)*Ra|

[0112] In one configuration, the algorithm includes the following steps.

[0113] 1. Two time points T5 and T2 are set as the earliest current zero crossing and the previous zero crossing, respectively. The additional time points are set within the sampling period T s The time points are set before and after each of these initial time points as a function of T. In total, there will be six time points in the set, T = {T1, T2, T3, T4, T5, T6}, where T1 = T2 - T s , T3=T2+T s , T4=T5-T s , and T6=T5+T s It is.

[0114] 2. Vwe-ie(t) is sampled at each time instant in the set to generate a set of voltages V={V1, V2, V3, V4, V5, V6}, where V n =V we-ie (T n ).

[0115] 3. I(t) is sampled at each time point in the set from device commands to the outputs or from output current monitors to generate a set of currents I={I1, I2, I3, I4, I5, I6}, where I n =I(T n ).

[0116] 4. Access resistance R est The set of values ​​of Ra is the last known value of Ra, Ra0, and the delta value δ Ra The value Ra0 can come from an estimate, a pre-stimulus measurement, or the last dynamic measurement, i.e., the previous result of this algorithm. In total, there will be three resistance values ​​in the set, R est={Ra1,Ra2,Ra3}, where Ra1=Ra0-δ Ra , and Ra3 = Ra0 + δ Ra It is.

[0117] 5. Calculate the set of relative slopes in the sampled voltages bounded by T3 and T1 (or T6 and T4) for each resistance value as follows: a. S={|(V3-I3*r)-(V1-I1*r)|:r∈R est}

[0118] 6. R a Set R (in the previous algorithm we set R = R) equal to the element of r that produces min{S}. This access resistance is then used in subsequent calculations of R and future decisions.

[0119] 7. Calculate the peak-to-peak voltage at the current zero crossing point as follows: a. Vpp=|V2-I2*Ra|+|V5-I5*Ra|

[0120] In some configurations, the algorithm for a low frequency biphasic waveform includes the following steps.

[0121] 1. A set of eight time points is defined across the biphasic waveform as follows: a.T 0,6 = current zero crossing time, where T0 is from the previous cycle and T6 is from the current cycle b. T 1,7 = the beginning of the first phase current plateau, where T1 is from the previous cycle and T7 is from the current cycle c. T2 = End of the first phase current plateau d. T3 = current zero cross time e. T4 = Beginning of the second phase current plateau f. T5 = End of second phase current plateau

[0122] 2. V we-ie (t) is sampled at each time instant in the set to generate a set of voltages V={V1, V2, V3, V4, V5, V6, V7}, where V n =V we-ie (T n ).

[0123] 3. I(t) is sampled at each time point in the set from device commands to the outputs or from output current monitors to generate a set of currents I={I1, I2, I3, I4, I5, I6, I7}, where I n =I(T n ).

[0124] 4. Cdl for the first and second phases are determined from Cdl=Q / (V3-V0) and Q / (V6-V3), respectively, where Q is known from the device command to the output or from the output current monitor and phase times.

[0125] 5. Ra for the first and second phases is determined from Ra=(V2-V4) / (I2-I4) and (V7-V5) / (I7-I5).

[0126] 6. Vcdl (Vpp elsewhere) for the first and second phases is determined from Vcdl=V3-V0 and V6-V3, respectively.

[0127] The aforementioned algorithms can evaluate Ra and Vpp every half cycle, thereby indirectly evaluating the capacitance of the working electrode. In some configurations, it is desirable to evaluate these parameters every half cycle. In some configurations, it may be desirable to evaluate these parameters less frequently, such as 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, or more periods. In some configurations, it may be desirable to evaluate these parameters on demand for evaluation by an interested party, such as a patient, physician, device representative, or other party, or at specific times, such as before device power off, after device power tone, and at some set period. In some configurations, it may be desirable to observe how these parameters change over time, including total run time, total implant time, total number of periods, or other time window of interest. In some configurations, the algorithms can be applied in post-processing, such as during examination by a device programmer or physician, for example, rather than in real time.

[0128] In some configurations, it is desirable to use these measured parameters to modify the waveform delivered. The following examples illustrate the use of such parameters to change the waveform delivered by the stimulation engine, or as a safety or mitigation mechanism to ensure proper operation of the stimulation engine.

[0129] Example 1a: To ensure that the electrodes are not used beyond capacity, the current is controlled based on the real-time voltage across the capacitor, ie, the current is controlled so that Vcdl does not increase beyond a limit.

[0130] Example 1b: Vary the bias to maximize Cdl to ensure that the electrodes are used at maximum capacity.

[0131] Example 1c: To ensure maximum delivery of bipolar current, to achieve maximum combination of CDL and capacitance, to equalize contact capacitance, to automatically control total bias at higher levels, use CDL of each WE in the pair and split bias between two contacts.

[0132] Example 2a: Use real-time UA measurements to obtain an indication of the health of the surrounding tissue and limit current based on this parameter.

[0133] Example 2b: Another option is to duty cycle the current over a period of hours or days, assuming the tissue heals, the rate of which may depend on the profusion rate of the surrounding tissue.

[0134] Example 3: Modify waveform morphology (current profile and duration) to optimize charge and amplitude and bias to deliver effective stimulation with minimal impact on the electrode and surrounding tissue by maximizing or minimizing CDL and then using RA as a tissue health indicator.

[0135] Each multiplexer of the stimulus engine (e.g., VRE, SRCA MUX, SRCB MUX, etc.) may similarly be monitored to ensure proper operation. For example, VOS (FIG. 12) may be monitored to check the current to and from each multiplexer. Out-of-range values ​​(e.g., excessive current drawn by the multiplexer power supply) may indicate a failure of one or more channels of the multiplexer (or the entire multiplexer).

[0136] The WEMX mechanism refers to the use of two multiplexers (e.g., SRCA MUX, SRCB MUX in FIG. 12) to mitigate the risk of multiplexer failure or low-level leakage. By routing the therapeutic current waveform through two multiplexers before reaching the selected electrode (and the patient), both multiplexers should be free from causing low-level leakage.

[0137] The CBSW mechanism refers to utilizing the capacitor bypass switches ULFSWA and ULFSWB to perform a self-test on the stimulation engine circuitry. For example, in one embodiment, the capacitor bypass switch ULFSWA or ULFSWB is activated or deactivated while the multiplexers SRCA MUX, SRCB MUX short the selected working electrodes together to create a test loop. The stimulation engine then attempts to send a DC signal through the test loop to determine whether the capacitor bypass switch and bypass capacitor, as well as other circuits in the loop, are operating properly.

[0138] The MCU mechanism, as discussed above, refers to providing redundant MCUs (e.g., a main MCU and a safety MCU). In some cases, each MCU may maintain separate peripherals to improve reliability, and in some cases may share peripherals or share data from those peripherals.

[0139] The IESW mechanism refers to the provision of multiple DC switches at the indifferent electrodes. Such fault tolerance ensures that the patient is not exposed to the Vie signal at the can during AC mode operation.

[0140] The VSR mechanism refers to the placement of multiple series resistors on the Vref signal. Such fault tolerance ensures that in the extremely unlikely event of a Vref failure that would result in current flowing out of the input, the series resistors limit such current.

[0141] The VRMX mechanism refers to providing a separate multiplexer VRE to access and sense the reference voltage Vre on selected electrodes E01-E16. The multiplexer is configured to disconnect the Vref amplifier from the working electrodes (e.g., selected electrodes E01-E16) when the Vref amplifier is not in use.

[0142] The BCAP mechanism refers to dual blocking capacitors CBA, CBB (one for each amplifier SRCA, SRCB) that ensure that the cans can be switched into the stimulation path during AC stimulation mode to ensure that no DC current is provided during AC stimulation mode, as described in more detail herein.

[0143] The ESD mechanism refers to a stimulus engine that includes one or more electrostatic discharge (ESD) paths to sink unwanted electrostatic energy. Each ESD path may include a diode to an internal voltage rail and another diode to an internal ground rail, where the voltage between the rails is limited by a clamping diode of a selected voltage. This configuration of diodes is called a steering diode configuration and must accommodate both bipolar and unipolar operation within a variable voltage range, so that parasitic diodes on the output circuit, whose operating voltage is assumed to be tied to the variable voltage range, are protected. Each steering diode can be converted into a series pair, so that if one diode fails, the other diode is still operational. As a further circuit optimization, if multiple channels are present, the second series can be grouped into one diode device to reduce the number of components.

[0144] The CALR mechanism refers to providing a calibration load (e.g., CAL in FIG. 12 ). The calibration load can be used in combination with the current generators SRCA, SRCB, TRIM-A, TRIM-B and the VIE current sensing monitor to configure a current generator.

[0145] The WEAM mechanism refers to the WEAM monitor, which compares the output voltages of the two amplifiers CSA, CSB of the stimulus engine. Since the stimulus engine operates in a bipolar state, the controller expects to see symmetrical values ​​(e.g., the voltage of one amplifier should be equal to the same or opposite voltage of the other amplifier), or values ​​that differ by a small known offset.

[0146] Additionally, the ACALx mechanism refers to the current output being calibrated by switching a calibration load CAL into the output path of the stimulation engine and monitoring the current through the calibration load (e.g., with a current sensor Iie). By determining the difference between the measured current and the programmed or desired current, an offset or calibration adjustment can be made to the stimulation engine. For example, the input to the DAC can be increased or decreased by an offset value to compensate for such difference.

[0147] Dual switches for redundancy in the capacitors CBA, CBB bypass switches ULFSW can provide an additional layer of security. Series switches IESW1, IESW2 to the IE can also provide an additional layer of safety to protect against AC transmission to the indifferent electrode of the stimulation engine (e.g., metal housing or can). Two high impedance resistors VR1, VR2 can be provided to protect against unexpected amplifier failure. If a failure in the Vref system is detected, a multiplexer VRE can be utilized to disable the electrode multiplexers SRCA MUX, SRCB MUX. An amplifier calibration load can be used in combination with a current generator to calibrate the voltage amplifier. For example, an amplifier that directs current to the IE should accurately output the desired current. When the stimulation engine is powered up, the stimulation engine can switch to the calibration resistor to route current to the calibration resistor, IE, and current sensor (Iie) to ensure that the amplifier path is operating properly. Such a circuit can also function as a discharge path for charge recovery. When in AC mode, two forms of charge recovery are possible. During active recovery, as discussed above, a pulse of the desired amplitude is output, then a fractional pulse of longer duration is sent. For example, a 1 microsecond stimulation pulse can be delivered, then an 8 microsecond recovery pulse can be applied. The same amount of current is sent in the opposite direction. During passive recovery, a stimulation pulse is sent to the electrode, then a capacitor or resistor is switched into the circuit for recovery.

[0148] FIG. 22 illustrates one embodiment of an output multiplexer U20. The multiplexer U20 may be used by the stimulation engine to select an electrode that receives a stimulation pulse, an electrode that forms a return path for the stimulation pulse, and / or an electrode that functions as a reference electrode. The multiplexer U20 may be used as any one or more of the VRE, SRCA MUX, SRCB MUX, IESW1, and / or IESW2 of FIG. 12. Additionally, the multiplexer U20 includes a back-bias diode D5 that prevents back-biasing to the multiplexer. Back-biasing may result in undesirable DC current flowing in the multiplexer, and therefore the back-bias diode D5 ensures that the multiplexer U20 does not enter a state where it may be back-biased. The back-bias diode D5 may be provided with any one or more of the VRE, SRCA MUX, SRCB MUX, IESW1, and / or IESW2 components of FIG. 12.

[0149] Figure 23 shows various instrumentation amplifiers U1A, U1B, U33A, U33B, U3A, U3B, U5A, U5B that may be used to measure the Vref, Vwe1, Vwe2, and IE voltages of the stimulus engine. The voltages are read by one or more of the main and safety MCUs of Figure 12. Test points TP1-TP4 correspond to the buffered Vre, VweA, VweB, and Vie voltages.

[0150] FIG. 24 shows the various current generators, rebalance switches, trim DACs, polarity / zero circuits, and current setting circuits. The current setting circuit has two DACs U7 and U8 (corresponding to the SRCA DAC and SRCB DAC in FIG. 12). Each DAC is set to a different fixed output voltage level. The switch U21 in the polarity / zero circuit (corresponding to the CFG in FIG. 12) can quickly switch between the two DAC outputs and sends the selected DAC output to the amplifiers U13A, U13B (corresponding to the SRCA and SRCB in FIG. 12). The switch U21 can switch between the DAC outputs much faster than the DAC can change its output in response to a changing input. Thus, the switch U21 allows the stimulus engine to provide very fast AC pulses (e.g., 100 Hz, 250 microsecond pulse width, etc.). The two trim DACs U19, U6 (corresponding to the TRIMB DAC and TRIMA DAC in FIG. 12) can trim the amplifiers in various ways. For example, each trim DAC U19, U6 can be used to set the desired bias current for each current source when in ULF / DC mode. In addition, each trim DAC U19, U6 can also compensate for any offset voltages present in the op-amps (e.g., U13A, U13B) used to generate the currents. Furthermore, rebalance switches U15A, U15B (corresponding to RBSWA and RBSWB in FIG. 12) can be used to disconnect the IE from the can and use it as a virtual ground to recover charge from the capacitor when in AC mode. In ULF / DC mode, the IE can be used for bias currents and also functions as a virtual ground.

[0151] The Stimulation Engine of FIG. 12 includes an indifferent electrode and an instrument for applying and controlling an active voltage on the indifferent electrode of the Stimulation Engine. A digital-to-analog converter VIE DAC is controlled to generate the indifferent electrode voltage (or IE drive or virtual ground). The VIE DAC output passes through a buffer or voltage follower DRV. The Stimulation Engine can sense the current to the indifferent electrode using a current monitor Iie. An amplifier can step up the voltage, which is then analyzed by the processor of the main MCU, the safety MCU, or both to ensure it is within range.

[0152] FIG. 25 illustrates one embodiment of an adjustable stimulation power delivery circuit with fault detection used by the stimulation engine of FIG. 12. The circuit shown can be used to sense the current used to drive the multiplexer of the stimulation engine. A boost power supply generates a high voltage signal Vboost for tissue stimulation. The Vboost signal is downregulated to generate the Vstim signal. Vboost is generated in a switching regulator and can be noisy. The noise is reduced by adding a secondary regulator to generate Vstim. A DAC U2 is used to control the Vstim signal to optimize power. A fault detector (VSTIM overvoltage hard fault) can determine if the Vstim signal is above a desired level. If so, the fault detector turns off the Vstim signal. The multiplexer is fed with the VOS+ and VOS- signals and the current is sensed in resistors R56, R57 and amplified in current sense amplifier U16. Comparator U32 can determine if the Vstim signal is too high or not at the desired level. If so, a fault is sent to the microprocessor's main MCU, the safety MCU. The microprocessor can also be used to create faults to test the fault detection circuitry. For example, the microprocessor can set the regulator output too high to verify that the fault detection circuitry is operating correctly.

[0153] The above description and examples are provided to illustrate the present disclosure according to various embodiments and are not intended to be unduly limiting. The headings provided herein are for organizational purposes only and should not be used to limit the embodiments. Each of the disclosed aspects and examples of the present disclosure may be considered individually or in combination with other aspects, examples, and variations of the present disclosure. In addition, unless otherwise specified, any of the steps of the method of the present disclosure are not limited to any particular order of execution. The references cited herein are incorporated by reference in their entirety.

[0154] While the methods and devices described herein may be susceptible to various modifications and alternative forms, specific examples of which have been shown in the drawings and are described in detail herein, it is to be understood, however, that the disclosed embodiments are intended to cover modifications, equivalents, and alternatives falling within the spirit and scope of the various embodiments as described herein and in the appended claims.

[0155] Depending on the embodiment, one or more acts, events, or functions of any of the algorithms, methods, or processes described herein may be performed in a different order, or may be added, combined, or omitted entirely (e.g., not all acts or events described may be required to implement an algorithm). In some examples, acts or events may be performed simultaneously rather than sequentially, for example, via multithreading, interrupt processing, or multiple processors or processor cores, or on other parallel architectures.

[0156] The use of sequential or chronological language such as "then," "next," "after," "thereafter," and the like, unless specifically stated otherwise or understood otherwise within the context in which it is used, is generally intended to facilitate the flow of the text and is not intended to limit the order of actions to be performed.

[0157] The various exemplary logic blocks, modules, processes, methods, and algorithms described in connection with the embodiments disclosed herein may be implemented as electronic hardware, computer software, or a combination of both. To clearly illustrate this interchangeability of hardware and software, the various exemplary components, blocks, modules, operations, and steps have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends on the particular application and design constraints imposed on the overall system. The described functionality may be implemented in various ways for each particular application, and such implementation decisions should not be interpreted as causing a departure from the scope of the present disclosure.

[0158] The various example logic blocks and modules described in connection with the embodiments disclosed herein may be implemented or performed by a machine, such as a processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. The processor may be a microprocessor, but in the alternative, the processor may be a controller, a microcontroller, or a state machine, combinations thereof, and the like. The processor may be implemented as a combination of computing devices, for example, a combination of a DSP and a microcontroller, multiple microprocessors, one or more microprocessors in combination with a DSP core, or any other such configuration.

[0159] The blocks, operations, or steps of a method, process, or algorithm described in connection with the embodiments disclosed herein may be embodied directly in hardware, in a software module executed by a processor, or in a combination of the two. The software module may reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, a hard disk, a removable disk, an optical disk (e.g., a CD-ROM or DVD), or any other form of volatile or non-volatile computer readable medium known in the art. The storage medium may be coupled to the processor such that the processor can read information from, and write information to, the storage medium. In the alternative, the storage medium may be integral to the processor. The processor and the storage medium may reside in an ASIC. The ASIC may reside in a user terminal. In the alternative, the processor and the storage medium may reside as discrete components in a user terminal.

[0160] Conditional language used herein, such as "may," "might," "could," "for example," among others, is intended to generally convey that some examples include certain features, elements, and / or conditions, while other examples do not include certain features, elements, and / or conditions, unless specifically stated otherwise or understood otherwise within the context in which it is used. Thus, such conditional language is not generally intended to imply that features, elements, blocks, and conditions are in any way required by one or more examples, or that one or more examples necessarily include logic for determining whether those features, elements, and / or conditions are to be included or performed in any particular embodiment, with or without author input or prompting.

[0161] Although the methods disclosed herein may include specific actions initiated by a practitioner, the methods may also include any third-party direction of those actions, either explicitly or implicitly. For example, an action such as "place electrodes" includes "instruct placement of electrodes."

[0162] Ranges disclosed herein encompass any overlaps, subranges, and combinations thereof. Phrases such as "up to," "at least," "greater than," "less than," "between," and the like, are inclusive of the recited number. Numbers preceded by terms such as "about" or "approximately" are inclusive of the recited number and should be interpreted in the context (e.g., as precisely as reasonably possible under the circumstances, e.g., ±5%, ±10%, ±15%, etc.). For example, "about 1 hour" includes "1 hour." Phrases preceded by terms such as "substantially" are inclusive of the recited phrase and should be interpreted in the context (e.g., as much as reasonably possible under the circumstances). For example, "substantially vertical" includes "vertical." Unless otherwise specifically stated, all measurements are at standard conditions, including temperature and pressure. The phrase "at least one" is intended to require at least one item from the subsequent list, rather than one type of each item from each item in the subsequent list. For example, "at least one of A, B, and C" can include A, B, C, A and B, A and C, B and C, or A, B, and C. [Explanation of symbols]

[0163] CBA, CBB Blocking Capacitors D5 Back bias diode DRV Voltage Follower E01~E16 Electrode Iie current sensor IESW1, IESW2 Series IE Switch RBSWA, RBSWB Rebalance switch SRCA, SRCB Current Generator SRCA MUX, SRCB MUX Multiplexer TRIMA DAC, TRIMB DAC U1A, U1B, U33A, U33B, U3A, U3B, U5A, U5B Instrumentation Amplifiers U7, U8 DAC U13A, U13B Op-amps U15A, U15B Rebalance Switch U19, U6 Trim DAC U20 Multiplexer U21 Switch ULFSWA, ULFSWB Capacitor bypass switch VIE DAC Digital to Analog Converter VR1, VR2 High impedance resistors

Claims

**Claim 1** A neuromodulation device configured to operate in a plurality of waveform generation modes, comprising: a power supply; a control unit communicating with the power supply; a bipolar current generator communicating with the control unit and an input of a switching unit; a plurality of electrodes each communicating with a respective output of the switching unit, the switching unit being configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit; the bipolar current generator being configured to deliver an alternating current to at least one active electrode of the plurality of electrodes during a first waveform generation mode, and the bipolar current generator being further configured to deliver a direct current to the at least one active electrode during a second waveform generation mode; a reference electrode configured to provide a return path for the alternating current, the direct current, or both; the control unit being configured to detect at least one fault event and, in response to the detected at least one fault event, prevent, modify, or stop the operation of the bipolar current generator. **Claim 2** The neuromodulation device of claim 1, wherein the at least one fault event includes that an actual stimulation current is different from a desired stimulation current, and the actual stimulation current is the alternating current or the direct current. **Claim 3** The neuromodulation device of claim 1, wherein the at least one fault event includes that a monitored current signal from the power supply to the switching unit exceeds a predicted current amount. **Claim 4** The neuromodulation device of claim 1, wherein the at least one fault event includes a real-time determination that at least one of a resistance or a capacitance of the at least one active electrode is not equal to a predicted resistance or a predicted capacitance of the at least one active electrode. **Claim 5** The neuromodulation device of claim 1, wherein the at least one fault event includes a real-time determination that a peak-to-peak voltage of the at least one active electrode exceeds a predicted voltage of the at least one active electrode. **Claim 6** The neuromodulation device of claim 1, wherein the at least one fault event includes that a blocking capacitor is not functioning properly.

7. The neurostimulation device of claim 1, wherein the direct current includes an anode current and a cathode current, and the at least one fault event includes that the anode current is not (1) equal to the cathode current and (2) opposite in sign to the cathode current.

8. The neurostimulation device of claim 1, wherein the direct current includes an anode current and a cathode current, and the at least one fault event includes that the anode current is not (1) less than a threshold amount different from the cathode current and (2) opposite in sign to the cathode current.

9. The neurostimulation device of claim 1, wherein the at least one fault event is any of the fault events described herein.

10. A neurostimulation device configured to operate in a plurality of waveform generation modes, a power supply, a control unit in communication with the power supply, a bipolar current generator in communication with the control unit and an input of a switching unit, a plurality of electrodes each in communication with a respective output of the switching unit, the switching unit being configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, the bipolar current generator being configured to deliver an alternating current to at least one active electrode of the plurality of electrodes during a first waveform generation mode, and the bipolar current generator being further configured to deliver a direct current to the at least one active electrode during a second waveform generation mode, the plurality of electrodes, and an indifferent electrode configured to provide a return path for the alternating current, the direct current, or both comprising, the control unit being configured to monitor a current flowing to the power supply of the switching unit and deactivate the bipolar current generator if the monitored current violates a threshold condition.

11. The neurostimulation device of claim 10, wherein violating the threshold condition corresponds to the monitored current exceeding a threshold level.

12. The neurostimulation device of claim 10, wherein violating the threshold condition corresponds to the monitored current falling below a threshold level.

13. The neuromodulation device according to claim 10, wherein the switching unit comprises a multiplexer.

14. The neuromodulation device according to claim 10, further comprising an anti - bias diode communicating with at least one output of the switching unit, wherein the anti - bias diode is configured to prevent the anti - bias of the switching unit at at least one output.

15. A neuromodulation device configured to operate in a plurality of waveform generation modes, a power supply, a control unit communicating with the power supply, a bipolar current generator communicating with the control unit and an input of the switching unit, a plurality of electrodes each communicating with a respective output of the switching unit, wherein the switching unit is configured to provide electrical communication between the bipolar current generator and a selected one of the plurality of electrodes in response to a control signal from the control unit, the bipolar current generator being configured to deliver an alternating current to at least one active electrode during a first waveform generation mode, and the bipolar current generator being further configured to deliver a direct current to the at least one active electrode during a second waveform generation mode, a plurality of electrodes, a reference electrode configured to provide a return path for the alternating current, the direct current, or both, a bipolar current generator calibration unit comprising a calibration load and a calibration load switch, wherein the control unit activates the calibration load switch to conduct current from the bipolar current generator to the calibration load, measures the current conducted to the calibration load, and is configured to calibrate the bipolar current generator in response to the measured current, a bipolar current generator calibration unit comprising a neuromodulation device.

16. The neuromodulation device according to claim 15, wherein the calibration load comprises a resistor.

17. The neuromodulation device according to claim 15, further comprising a current sensor configured to measure the current conducted to the calibration load.

18. The neuromodulation device according to claim 15, wherein calibrating the bipolar current generator comprises adjusting the value of a control signal transmitted to the bipolar current generator.

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