Patent Publication Number: US-2016235329-A1

Title: Nerve bundle cuff including electrodes and transducers

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority to and benefit of U.S. Provisional Patent Application No. 62/115,976 filed on Feb. 13, 2015 and titled “NERVE BUNDLE CUFF INCLUDING ELECTRODES AND TRANSDUCERS,” which is herein incorporated by reference in its entirety. 
    
    
     BACKGROUND OF THE DISCLOSURE 
     Electrodes can be implanted into target tissue to record from and stimulate the target tissue. For example, depth electrodes can be implanted into the brain for the treatment of Parkinson&#39;s disease and epilepsy. The patient&#39;s body can encapsulate the electrodes over time with fibrous tissue, reducing their efficacy. 
     SUMMARY OF THE DISCLOSURE 
     According to one aspect of the disclosure, a tissue interface device includes a biocompatible polymer backing. The device also includes an electrode array that is coupled to the biocompatible polymer backing. The electrode array includes one or more electrode shafts that project substantially perpendicular to a plane of the biocompatible polymer backing. Each of the one or more electrode shafts include an electrode site. The device also includes one or more ultrasound transducers coupled to the biocompatible polymer backing. 
     In some implementations, each of the one or more electrode shafts include a plurality of electrode sites distributed along a length of the respective one or more electrode shafts. The one or more ultrasound transducers can include at least one of a bulk ferroelectric ceramic, a crystal ferroelectric, a ferroelectric polymer, a capacitive micromachined ultrasonic transducer (cMUT), a piezoelectric micromachined transducer (pMUT), and an electrostrictive polymer. 
     In some implementations, the device includes a controller that is configured to energize the one or more ultrasound transducers at a first frequency for stimulating a target and at a second frequency for imaging the target. In some implementations, the controller is also configured to record an electrical signal detected at the electrode site. 
     In some implementations, the device includes a rechargeable battery. The device can include an induction coil to wirelessly receive energy from an external source and provide the received energy to the rechargeable battery. 
     In some implementations, the electrode array includes between about 2 and about 64 electrode shafts. In some implementations, the biocompatible polymer backing is a flexible cuff configured to wrap around a nerve. 
     According to another aspect of the disclosure, a method includes coupling a tissue interface device to a target tissue. The tissue interface device includes a biocompatible polymer backing and one or more electrodes that are coupled to the biocompatible polymer backing. The device also includes one or more ultrasound transducers that are coupled to the biocompatible polymer backing. The method also includes delivering a stimulation signal to the target tissue via the one or more electrodes and imaging the target tissue via the one or more ultrasound transducers. 
     In some implementations, the method also includes ultrasonically stimulating the target tissue via the one or more ultrasound transducers. The method can include imaging the target tissue via the one or more ultrasound transducers with a first frequency of ultrasonic energy and ultrasonically stimulating the target tissue via the one or more ultrasound transducers with a second frequency of ultrasonic energy different than the first frequency of ultrasonic energy. 
     In some implementations, imaging the target tissue includes detecting a scar formation on the target tissue. In some implementations, the tissue interface device is configured as a cuff and coupling the tissue interface device to the target tissue further includes wrapping the tissue interface device around the target tissue. 
     In some implementations, the one or more electrodes each include an electrode shaft projecting substantially perpendicular to a plane of the biocompatible polymer backing and each electrode shaft includes an electrode site. In some implementations, each electrode shaft includes a plurality of electrode sites distributed along a length of the electrode shaft. 
     In some implementations, the tissue interface device includes between about 2 and about 64 electrode shafts. In some implementations, the target tissue is neural tissue. In some implementations, the one or more ultrasound transducers include at least one of a bulk ferroelectric ceramic, a crystal ferroelectric, a ferroelectric polymer, a capacitive micromachined ultrasonic transducer (cMUT), a piezoelectric micromachined transducer (pMUT), and an electrostrictive polymer. The method can also include wirelessly charging a battery of the tissue interface device. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The skilled artisan will understand that the figures, described herein, are for illustration purposes only. It is to be understood that in some instances various aspects of the described implementations may be shown exaggerated or enlarged to facilitate an understanding of the described implementations. In the drawings, like reference characters generally refer to like features, functionally similar and/or structurally similar elements throughout the various drawings. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the teachings. The drawings are not intended to limit the scope of the present teachings in any way. The system and method may be better understood from the following illustrative description with reference to the following drawings in which: 
         FIG. 1  illustrates an example system for stimulating and monitoring a target tissue with a tissue interface. 
         FIG. 2  illustrates the example tissue interface illustrated in the system of  FIG. 1 . 
         FIGS. 3A and 3B  illustrate an example cuff in a flat and rolled configuration, respectively. 
         FIGS. 4A and 4B  illustrate another example tissue interface in a ribbon configuration with integral ultrasound transducers and electrodes. 
         FIG. 5  illustrates a flow chart of an example method for stimulating target tissue with a tissue interface. 
     
    
    
     DETAILED DESCRIPTION 
     The various concepts introduced above and discussed in greater detail below may be implemented in any of numerous ways, as the described concepts are not limited to any particular manner of implementation. Examples of specific implementations and applications are provided primarily for illustrative purposes. 
     The present disclosure describes systems and methods for recording and stimulating neural and other tissue. The disclosure describes a tissue interface that can be configured as a cuff or a ribbon and includes a plurality of electrodes and ultrasound transducers. The tissue interface is configured to electrically and ultrasonically stimulate tissue, such a muscle tissue and neural tissue. The tissue interface is also configured to monitor the target tissue by recording electrical activity of the target tissue with one or more of the electrodes and image the target tissue with one or more of the ultrasound transducers. 
       FIG. 1  illustrates an example system  100  for stimulating and monitoring tissue. The system  100  includes tissue interface  102  in a cuff configuration (also referred to as a cuff  102 ) that is wrapped around a nerve  104 , which is also referred to as the target tissue  104 . The cuff  102  includes a plurality of ultrasound transducers  106  and a plurality of electrodes  108 . The nerve cuff  102  is coupled to and controlled by a controller  110 . The controller  110  is powered by a power source  112  and includes a microprocessor  114  that controls an electrode stimulator and recorder (ESR)  116  and a transducer stimulator and recorder (TSR)  118 . The data recorded by the ESR  116  and the TSR  118  can be stored in memory  120  for later transfer and analysis. 
     The controller  110  of the system  100  controls the stimulation and monitoring of the tissue  104 . In some implementations, the controller  110  is a hermetically sealed device that is configured for chronic implantation near the target tissue  104 . In other implementations, the controller  110  is a handheld device or computer that resides outside of the patient and communicates wirelessly or via a wired connection to the cuff  102 . The controller  110  includes one or more microprocessors  114  that control the function of the ESR  116  and the TSR  118 . The microprocessor  114  can be any type of single or multi-core processor or special purpose logic circuitry such as an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit). In some implementations, the controller  110  outputs data to other devices for analysis. The controller  110  can communicate with the other devices wirelessly or through a wired connection. 
     The ESR  116  of the controller  110  generates electrical stimuli that are used to stimulate the tissue  104  at each or a subset of the electrodes  108 . For example, the ESR  116  can generate electrical pulses or waves, and can control the frequency, pulse width, signal shape (e.g., square and sinusoidal shaped), amplitude or additional properties of the stimulation, such as selecting which electrodes to stimulate, which to read out, and which ultrasound transducers to actuate. The ESR  116  can generate a stimulation signal with a frequency between about 10 Hz and about 25 kHz, between about 10 Hz and about 10 kHz, between about 100 Hz and about 1 kHz, or between about 100 Hz and about 500 Hz. The ESR  116  also includes one or more analog to digital converters (ADC) that converts the measured electrical activity from the tissue  104  into a digital signal that can be stored in memory  120 . The ADCs of the ESR  116  can sample the signal measured by each of the plurality of electrodes  108  at a frequency between about 10 Hz and about 10 kHz, between about 10 Hz and about 5 kHz, between about 10 Hz and about 1 kHz, between about 50 Hz and about 500 Hz, or between about 50 Hz and about 250 Hz. The TSR  118  of the controller  110  generates electrical stimulus that is used to stimulate the transducers  106  and generate ultrasonic energy. 
     The TSR  118  is configured to generate pulses that cause the transducers  106  to resonate and generate ultrasonic energy between about 0.5 MHz and about 20 MHz, between about 5 MHz and about 15 MHz, or between about 10 MHz and about 15 MHz. In some implementations, the TSR  118  is configured to generates pulses that cause the transducers  106  to resonate and generate ultrasonic energy at a first frequency for stimulating a target and at a second frequency for imaging the target tissue. For example, the stimulation frequency may be a relatively high frequency (e.g., above 10 MHz) when compared to the second frequency used for imaging the target tissue. In some implementations, the frequency for imaging the target tissue is selected such that the ultrasound wave has a wavelength similar to or less than the resolution to needed to image the target tissue. For example, a 5 MHz ultrasound signal has a wavelength (λ) in water of about 0.3 mm using the equation λ=(speed of signal)/(frequency of signal). In some implementations, the ultrasound transducers  106  are used to image the changes that within the target tissue in response to the ultrasonic and/or electrical stimulation to the target tissue. In some implementations, the ultrasound transducers  106  are used to detect the presence of scar tissue that may accumulate around the tissue interface  102  over time. For example, the increase in the acoustic mismatch between the ultrasound transducer  106  and the tissue target can result in a larger echo return, which can signal the development of scar tissue of the tissue target. 
     The controller  110  of the system  100  also includes a power source  112 . When the controller  110  is implanted into a patient, the power source  112  is a battery. In implementations where the controller  110  is external the to the patient, the power source  112  can be a battery or the controller  110  may be plugged into an AC power source (e.g., a wall outlet). In some implementations, the battery of the power source  112  is rechargeable. For example, the controller  110  can include a plurality of induction coils that enable the battery to be wirelessly recharged after the controller  110  is implanted into the patient. 
     Still referring to  FIG. 1 , the system  100  also includes a cuff  102 . The cuff  102  is described further in relation to  FIGS. 2-4 , but as an overview the cuff  102  is formed from one or more layers of a biocompatible polymer, such as silicone, poly(dimethyl siloxane) (PDMS), polyurethane, polytetraflouroethylene (PTFE), polyethylene, polypropylene, PMMA, Ethylene-co-vinylacetate, poly(ethylene terphthalate), polysulphone, polyethyleneoxide, or any combination thereof. A surface of the cuff  102  includes a plurality of transducers  106  and a plurality of electrodes  108 . The electrodes  108  of the cuff  102  are configured to record and electrically stimulate the tissue  104 . The cuff  102  also includes a plurality of transducers  106  to ultrasonically stimulate and image the tissue  104 . In some implementations, one or more of the components and functions of the controller  110  can be incorporated into the cuff  102 . For example, the cuff  102  can include integrated circuits and other electronics that perform signal filtering, amplification, analog to digital conversion, and channel selection. In some implementations, the cuff  102  is self-contained and also includes the power source  112  (e.g., a rechargeable battery) and an antenna. The implanted cuff  102  can communicate wirelessly with the controller  110  or other device located external to the patient. The implanted, self-contained cuff  102  can also include an induction coil that enables a rechargeable battery to be recharged through magnetic coupling. 
       FIG. 2  illustrates the example cuff  102  of  FIG. 1  prior to implantation. The cuff  102  includes a plurality of transducers  106  embedded within a polymer backing  202 . The top layer of the polymer backing  202  can be machined to expose the face  206  of each of the transducers  106 . In other implementations, the polymer backing  202  is not machined to expose the face  206  of each of the transducers. For example, the polymer backing  202  can be configured to have approximately the same acoustic impedance as tissue so that the polymer backing  202  does not substantially affect the ultrasonic energy generated by the transducers. In other implementations the polymer substrate acts as an impedance matching layer improving the acoustic coupling between the ultrasound transducer and the surrounding tissue. The polymer backing  202  is a flexible, biocompatible material, such as silicone. In some implementations, the polymer backing  202  is manufactured with a shape memory such that the two tips  204  of the polymer backing  202  curl inward to roll around the target tissue. In some implementations, a shape memory alloy can be embedded in the cuff  102  to cause the cuff to wrap around the target tissue. 
     The cuff  102  also includes a plurality of electrodes  108 . As illustrated the plurality of electrodes  108  are configured as an electrode array  208 . The electrodes  108  of the electrode array  208  are configured as penetrating, depth electrodes. In some implementations, each of the depth electrodes contain a plurality of electrode sites along a length of the electrode shaft  210  of the electrodes  108 . For example, the depth electrode can include a plurality of electrode sites along the electrode shaft  210  of each of the depth electrodes to provide readings (and stimulations) at different depths in the target tissue. As illustrated, the cuff  102  includes  16  electrode shafts  210 . In other implementations, the cuff  102  includes between about 1 and about 256 electrode shafts  210 , between about 4 and about 144 electrode shafts  210 , between about 16 and about 100 electrode shafts  210 , or between about 16 and about 64 electrode shafts  210 . In some implementations, each electrode shaft  210  includes between about 1 and about 32 electrode sites, between about 1 and about 24 electrode sites, between about 1 and about 12 electrode sites, or between about 1 and about 6 electrode sites. The electrode shafts  210  project substantially perpendicular to a plane of the polymer backing  202 . 
     The electrodes  108  of the cuff  102  can include platinum, platinum-iridium alloy, gold, iridium oxide, PEDOT, silver chloride, or a combination thereof. The transducers  106  can include bulk ferroelectric ceramics (e.g., diced slabs of polycrystalline lead zirconium titanate (PZT) or lead magnesium niobate-lead titanate (PMN-PT)), barium titanate, aluminum nitride, zinc oxide, tourmaline, berlinite, quartz, lithium tantalite, potassium niobate, bismuth iron oxide, crystal ferroelectrics, ferroelectric or electrostrictive polymers (e.g., polyvinylidene fluoride (PVDF)), capacitive micromachined ultrasonic transducers (cMUTs), piezoelectric micromachined ultrasonic transducers (pMUTs). 
     In some implementations, the transducers  106  can be used to both image and to stimulate the tissue  104 . Stimulation of tissue, such as neurons, with ultrasonic energy from the transducers  106  can be advantageous in comparison to stimulating the tissue with only electrical energy from the electrodes  108 . For example, ultrasonic energy may travel through connective and other fibrous tissue better than electrical energy. Because the patient&#39;s body naturally encapsulates foreign objects with a fibrous tissue electrical stimulation may become less effective over time; however, the ultrasonic energy can still be effective in stimulating target tissue even after the cuff  102  is encapsulated by the patient&#39;s body. Also, the effective stimulation zone of the ultrasonic energy can extend to greater depths when compared to the propagation waveform of electrical energy, enabling the ultrasonic waveform to stimulation more tissue than the electrical energy. The frequency of the ultrasonic energy can be selected to provide a predetermined penetration profile of the ultrasonic energy. For example, high frequency ultrasonic energy has a higher absorption rate and cannot penetrate as deeply when compared to low frequency ultrasonic energy, which has a lower absorption rate. In some implementations, over time the ultrasonic energy may cause less damage to the tissue when compared to electrical energy. 
     In some implementations, it is advantageous to include both transducers  106  and electrodes  108 . For example, the electrodes  108  can be used to electrically stimulate the target tissue while the transducers  106  are used to image the target tissue. In another example where the target tissue is a nerve, the transducers  106  can be used to ultrasonically stimulate the nerve, and the electrodes  108  can be used to record the electrical potentials generated by the nerve in response to the ultrasonic stimulation. 
       FIGS. 3A and 3B  illustrate another example cuff  300  in a flat and rolled configuration, respectively. The cuff  300  includes a plurality of transducers  306  and a plurality of electrodes  308 . The electrodes  308  and the transducers  306  alternate along the length of the cuff  300 . The electrodes  308  of the cuff  300  are non-penetrating, flat electrodes. In some implementations, the electrodes  308  have a height between about 50 μm and about 5 mm, between about 250 μm and about 4 mm, between about 750 μm and about 3 mm, or between about 1 mm and about 2 mm. The electrodes  308  circular, square, rectangular, or other geometrically shaped face. The cuff  300  also includes a cutout  310  at each of the corners of the cuff  300 . The cutouts  310  are used to secure the cuff  300  to the tissue. For example, sutures can be used to suture the cuff  300  to the tissue at each of the cutouts. Alternatively, once the cuff  300  is rolled around the target tissue, the rolled configuration (as illustrated in  FIG. 3B ) can be maintained by suturing the two top cutouts  308  together and the bottom two cutouts  308  together. By increasing or decreasing the slack of the suture between the pair of cutouts, the diameter of the rolled cuff can be configured to a desired diameter. 
       FIGS. 4A and 4B  illustrate an example tissue interface  400  in a ribbon configuration with integral ultrasound transducers and electrodes. As described above in relation to the cuff configurations, the ribbon electrode  400  includes a plurality of transducers  406  and a plurality of electrodes  408 . In some implementations, the ribbon electrode  400  is wrapped around the tissue. In other implementations, the ribbon electrode  400  is configured to pass through the target tissue  402 . The ribbon electrode  400  can be passed through the target tissue  402  one or more times. 
     In some implementations, the tissue interfaces described herein are fabricated by coating a silicon wafer with a sacrificial layer, such as maltose. A first polymer layer is spin-coated onto the sacrificial layer and cured. A first metal layer that includes the electrodes and the transducers is then patterned onto the first polymer layer. The first metal layer can also include electrical traces and other circuitry, such as amplifiers and analog to digital converts. In some implementations, the tissue interface can include a plurality of metal layers separated by a dielectric material. For example, the tissue interface may include a first metal layer that acts as a routing layer and includes all of the traces and a second metal layer that includes the transducers and the electrodes. A second polymer layer can be spin-coated over the exposed first polymer layer and metal layer, encapsulating the metal layers. After the second polymer layer has cured, windows are made in the second polymer layer with laser ablation or other machining process to expose the faces of the transducers and electrodes. The completed tissue interface is removed from the silicon wafer by dissolving the sacrificial layer. 
       FIG. 5  illustrates a flow chart of an example method  500  for stimulating a target tissue. The example method  500  includes providing a tissue interface (step  502 ). The tissue interface is wrapped around the target tissue (step  504 ). The electrodes of the tissue interface are stimulated (step  506 ) and the ultrasound transducers of the tissue interface are activated (step  508 ). 
     As set forth above, the method  500  includes providing a tissue interface (step  502 ). The tissue interface can be any of the tissue interfaces described herein. For example, the tissue interface can be configured as a cuff electrode that is configured to wrap around a nerve or other neural tissue. In some implementations, the tissue interface is in a ribbon configuration and is designed to be inserted into the target tissue. The target tissue can, for example, be a muscle, central nervous tissue, or peripheral nervous tissue. The tissue interface includes a plurality of electrode sites and ultrasound transducers. In some implementations, the electrodes are disk or other configurations of a planar electrode. In other implementations, the electrodes are depth electrodes that include one or more electrode sites along the shaft of each of the depth electrodes. 
     The method  500  also includes wrapping the tissue interface around the target tissue (step  504 ). In some implementations, the tissue interface is physically secured to the target tissue by sutures, surgical glue, or clamps. For example, if a patient has a spinal injury that prevents the patient from activating a muscle, the tissue interface may be implanted around the nerve that innervates the muscle distal to the damaged neural tissue. The tissue interface can be used to stimulate the innervating nerve—bypassing the damaged portion of the nerve. 
     After implantation of the tissue interface the electrodes are stimulated (step  506 ) and the ultrasound transducers are activated (step  508 ). The electrodes of the tissue interface are activated by the ESR, which sends electrical pulses or waves to the electrodes to stimulate the target tissue. In some implementations, the ESR configures which of plurality of electrodes act as stimulating electrodes and which of the plurality of electrodes act as recording electrodes. Similarly, the TSR activates the ultrasound transducers to deliver ultrasonic energy to the target tissue. The ultrasound transducers are activated when the TSR sends a series of electrical pulses to the ultrasound transducers, which cause the ultrasound transducers to resonant. The frequency of the ultrasonic energy is controlled by the TSR and the frequency is selected to control the amount of penetration that the ultrasonic energy has into the target tissue. In some implementations, the ultrasonic energy is configured to elicit a response from the target tissue (e.g., activate a neuron) and in other implementations the ultrasonic energy is configured to provide an A-mode or B-mode ultrasound image of the target tissue. 
     The disclosed system and methods may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The forgoing implementations are therefore to be considered in all respects illustrative, rather than limiting of the invention.