Google Patentsopen access

Peripheral Neural Interface Via Nerve Regeneration To Distal Tissues — Massachusetts Institute Of Technology (US20250195243A1)

ABSTRACT

Abstract

At least partial function of a human limb is restored by surgically removing at least a portion of an injured or diseased human limb from a surgical site of an individual and transplanting a selected muscle into the remaining biological body of the individual, followed by contacting the transplanted selected muscle, or an associated nerve, with an electrode, to thereby control a device, such as a prosthetic limb, linked to the electrode. Simulating proprioceptive sensory feedback from a device includes mechanically linking at least one pair of agonist and antagonist muscles, wherein a nerve innervates each muscle, and supporting each pair with a support, whereby contraction of the agonist muscle of each pair will cause extension of the paired antagonist muscle. An electrode is implanted in a muscle of each pair and electrically connected to a motor controller of the device, thereby simulating proprioceptive sensory feedback from the device.

Description

RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No. 17/120,938, filed Dec. 14, 2020, which is a continuation of U.S. application Ser. No. 15/233,241, filed Aug. 10, 2016, now U.S. Pat. No. 10,898,351, issued Jan. 26, 2021, which is a divisional of U.S. application Ser. No. 14/520,766, filed Oct. 22, 2014, now U.S. Pat. No. 9,474,634, issued Oct. 25, 2016, which claims the benefit of U.S. Provisional Application No. 61/894,040, filed on Oct. 22, 2013, and U.S. Provisional Application No. 62/019,266, filed on Jun. 30, 2014. The entire teachings of the above applications are incorporated herein by reference.

BACKGROUND OF THE INVENTION

Recent advances in prosthetic limbs include the provision of multiple degrees of freedom as well as powered actuators that have the potential to provide substantially greater functionality than the passive devices that existed just a decade ago. Despite these engineering accomplishments, developers still struggle with the issue of how to provide the prosthesis user with methods for coordinating the simultaneous control of all of the joints that are involved with, for example, object manipulation in the upper extremity case, or standing and walking in the lower extremity case. This deficit was first apparent for upper extremity prostheses, which now can provide elbow function, wrist rotation, and hand opening and closing. Today's commercially available, upper-extremity prosthetic controllers make use of the EMG activity (electro-myographic activity generated by muscle contraction) of functional native muscles that are present in the amputee's residual limb. This approach allows for proportional control with minimal execution delay. When the EMG activity used for prosthetic control arises from a pair of antagonistic muscles that would normally move the homologous biological joint (e.g., the biceps and triceps controlling flexion and extension, respectively, of the prosthesis elbow joint), the neurally controlled EMG commands are completely intuitive and thus easy to master.

However, more commonly in practice, the same set of EMG signal sources are used to control additional prosthetic joints, and this requires that the command sources be switched among the assigned joints in a serial manner. The resulting motion for most activities is thus awkward, time consuming, and tedious, since it breaks up any compound arm and hand movement into serial positioning steps, resulting in poor utilization of powered prostheses. In the lower extremity, powered ankle and knee joints are just becoming available to the general population. However, commercial lower-extremity prostheses typically do not utilize EMG as a source of control signals. Artificial sensory and computational systems have been demonstrated to provide some degree of control over ankle and knee flexion and extension for powered leg prostheses (E. C. Martinez-Villalpando and H. M. Herr, “Agonist-antagonist active knee prosthesis: A preliminary study in level-ground walking,” Journal of Rehabilitation Research & Development (JRRD), vol. 46, no. 3, pp. 361-73, 2009; S. Au, J. Weber, and H. M Herr, “Powered Ankle-Foot Prosthesis Improves Walking Metabolic Economy,” IEEE Transactions on Robotics, vol. 25, no. 1, pp. 51-66, 2009; H. M. Herr and A. M. Grabowski, “Bionic ankle-foot prosthesis normalizes walking gait for persons with leg amputation,” Proceedings of the Royal Society B, vol. 279, no. 1728, pp. 457-464, February 2012; E. J. Rouse, L. M. Mooney, E. C. Martinez-Villalpando, and H. M. Herr, “A clutchable series-elastic actuator: design of a robotic knee prosthesis for minimum energy consumption,” Proceedings of the IEEE International Conference on Rehabilitation Robotics, 2013). It is well appreciated, however, that the next generation of devices should provide smooth, simultaneous volitional-neural control over several degrees of freedom, such as the knee, ankle and subtalar joints. In that case, simultaneous control of several degrees of freedom will require multiple sources of independent, reliable, and intuitive control that can best be obtained by interfacing with the amputee's extrinsic neural control.

The efficacy of using an EMG-based neural activity approach for achieving simultaneous control of multiple prosthetic joints has been demonstrated in principle by a technique now referred to as “Targeted Muscle Re-innervation,” or TMR (T. A. Kuiken, G. A. Dumanian, R. D. Lipschutz, L. A. Miller, K. A. Stubblefield, “The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee, Prosthetics and Orthotics International, vol. 28, pp. 245-53, 2004; T. A. Kuiken, “Targeted reinnervation for improved prosthetic function,” Physical Medicine and Rehabilitation Clinics of North America, vol. 17, no. 1, pp. 1-13, 2006). For transhumeral prosthetic control, for example, TMR utilizes the activity of all four of the arm trunk nerves. As a surgical procedure, each trunk nerve is mobilized from the brachial plexus, and each nerve is anastomosed to a separate division of the pectoralis major muscle of the chest. The nerves grow into and innervate their respective new muscle targets and can independently cause contractions of the respectively innervated pectoral muscle divisions. The four recorded muscle signals can then be assigned to prosthetic elbow, wrist, and hand functions according to the original natural hand control function of each of the translocated nerves. For example, hand closing is controlled by evoked EMG activity from the pectoral muscle division innervated by the median nerve, and hand opening is controlled by EMG activity from the muscle division innervated by the radial nerve. Essentially, the operator's brain performs the coordination of the prosthesis joints when a complex task is performed. Despite the laudable success of the original and ensuing demonstrations, the TMR approach has a few shortcomings; for instance, the native innervation of the pectoral muscle (or other selected host muscle) must be removed so that the normal activation of the host muscle by its native innervation does not interfere with that by the transferred nerves. Having to eliminate the functionality of any native tissue for the greater good is not optimal. There are also some limitations regarding how far away a given nerve can be moved in order to connect it to a suitable muscle target. Finally, the use of surface recorded EMG and contiguous muscle targets can lead to inconsistent signal amplitudes and objectionable channel crosstalk (T. A. Kuiken, M. M. Lowery, and N. S. Stoykov, “The effect of subcutaneous fat on myoelectric signal amplitude and cross-talk,” Prosthetics and Orthotics International, vol. 27, no. 1, pp. 48-54, 2003). This last issue has been addressed by using a large array of recording sites and performing substantial pattern recognition to interpret a user's intended movements unambiguously. Over time, however, it is still necessary to “re-tune” the system, which is a substantial inconvenience.

Therefore, there is a need for a method of reversing motor impairment of a human limb, and of restoring at least partial function of a human limb that overcomes or minimizes the above-referenced problems.

SUMMARY OF THE INVENTION

The invention generally is directed to a method of restoring at least partial function of a human limb, to reversing motor impairment of a human limb, to simulating proprioceptive sensory feedback from a device, and to simulate cutaneous sensory feedback from a device.

In one embodiment, the method of restoring at least a partial function of the human limb includes surgically removing from a surgical site at least a portion of an injured or diseased human limb from an individual, leaving intact at least one selected muscle from the damaged portion of the human limb, including at least one of blood vessels and nerves associated with that portion of the at least one selected muscle. The at least one selected muscle is transplanted into the remaining biological body of the individual and the at least one transplanted selected muscle, or associated nerve, is contacted with an electrode, whereby signals can be transmitted to and from at least one of the nerve and its associated transplanted muscle to thereby control a device linked to the electrode and extending from the surgical site, thereby restoring at least partial function of the human limb. Examples of suitable devices for use with the method of the invention include a prosthetic limb, an orthotic limb and an exoskeletal limb.

In a specific embodiment, and at least one patch of skin is dissected, wherein the patch of skin includes at least one nerve selected from the group consisting of an intact native sensory nerve and a new regenerative innervation nerve. The patch of skin is translocated onto a non-anatomical portion of the individual from which the limb was removed. The translocated patch is contacted with an external prosthetic socket of a prosthetic limb, the prosthetic socket including at least one component that provides mechanical stimulation to the translocated patch of skin. In another embodiment, that further includes the steps of contacting the nerve of the patch of skin with a nerve cuff, wherein the nerve cuff is linked to a controller. The nerve is selectively stimulated by actuating the nerve with the controller. In another embodiment, the nerve includes at least one sensory nerve selected from the group consisting of sural, saphenous, tibial, peroneal, median, ulnar, and radial nerves. In still one embodiment, contact in the nerves of the transplanted selected muscles with an electrode includes implanting electrode on the epimysium of the selected muscle or intramuscularly in the selected muscles.

In another embodiment, the method of reversing impairment of a human limb includes transecting a nerve associated with the impairment of the limb of an individual to thereby form proximal and distal ends of the transected nerve. The proximal and distal ends of the transected nerve are placed into proximal and distal ends of a microchannel array, thereby causing the nerve to regenerate through the microchannel array. Sensory afferent information of the regenerated nerve is recorded using sensing electrodes within a plurality of afferent microchannels of the microchannel array. Motor efferent information is stimulated to provide efferent motor stimulus to the nerve using stimulating electrodes within the plurality of efferent microchannels of the microchannel array. The stimulating electrodes are electrically connected to a motor controller of a device. The sensing electrodes are electrically connected a sensory controller of the device, wherein the sensor controller is linked to at least one sensor of the biological limb that detects application of at least one of position, velocity, acceleration, and force of the biological limb, and whereby the sensory controller transmits detection of the position, velocity, acceleration, and force of the biological limb to the motor controller, and whereby the motor controller applies electrical stimulation via the stimulating electrodes, thereby reversing impairments of the human limb.

In still another embodiment, the invention is directed to a method of restoring at least partial function of the human limb of an individual that includes dissecting at least one patch of skin from individual, translocating the patch of skin onto a non-anatomical portion of the individual, wherein the skin patch includes at least one nerve selected from the group consisting of an intact native nerve and a new regenerative innervation nerve, and contacting the translocated skin patch with an external device, the device including at least one component that provides mechanical stimulation to the translocated skin patch, thereby restoring at least partial function of the human limb.

In still another embodiment, the method of the invention includes reversing the impairment of an amputated limb, including inserting a distal end of at least one transected nerve of an amputated limb into a proximal end of a microchannel array, placing at least one member of the group consisting of skin and muscle end organ at the distal end of the microchannel array, thereby causing the nerve to regenerate through the microchannel array and to innervate the at least one end organ. Efferent motor information of the regenerated nerve is recorded using sensing electrodes within a plurality of afferent microchannels of the microchannel array. The regenerated nerve is stimulated with afferent sensory information using stimulating electrodes within a plurality of afferent microchannels of the microchannel array. The sensing electrodes are electrically connected to a motor controller of a device. The stimulating electrodes are electrically connected to a sensory controller of the device, wherein the motor controller is linked to at least one sensor of the device that detects application of at least one member selected from the group consisting of position, velocity, acceleration, and force of the device, and whereby the motor controller transmits detection of the position, velocity, acceleration, and force by applying electrical stimulation via the stimulating electrodes, thereby providing the individual with a sensation simulating sensory feedback from the device, and reversing impairment of the amputated limb.

In yet another embodiment of the invention, the method includes simulating proprioceptive sensory feedback from a device, including the steps of the mechanically linking at least one pair of agonist and antagonist muscles, wherein a nerve innervates each muscle. The at least one pair of agonist and antagonist muscles are supported with a support, whereby contraction of the agonist muscle of each pair will cause extension of the paired antagonist muscle. At least one electrode is implanted in at least one muscle of each pair, and the at least one electrode is electrically connected to a motor controller of the device, thereby stimulating proprioceptive sensory feedback from the device.

In another embodiment, the invention is a method for simulating cutaneous sensory feedback from the device, including steps of excising a skin segment from a biological body part of an individual, the skin segment including at least one of a native nerve and a regenerative nerve supply. The skin segment is linked to at least one muscle having a nerve supply. An electrode is implanted in the at least one muscle. The skin segment and actuator muscle are supported on a support. The at least one electrode is electrically connected to a sensory controller of a device, wherein the controller is linked to a sensor of the device that detects application of at least one of stress, strain, contact, pressure and sheer at the device, and whereby the controller transmits detection of the stress, strain, contact, pressure or sheer by contracting the actuator muscle within electrical stimulation via the electrode, thereby stretching the mechanoreceptor of the skin segment and providing the individual with a sensation stimulating cutaneous sensory feedback from the device.

This invention has many advantages. For example, Applicants' claimed invention provides a strategy for clinicians to follow when planning an amputation procedure so that the possibility to later obtain enhanced prosthetic control is maximized. Specifically, in the case of limb amputation, this strategy may include deriving multiple independent electrical signals, such as electromyographic signals, and neural recorded signals to command powered actuators within an external prosthesis. Further, artificial sensory information may be provided from the externally-controlled limb prosthesis back to the amputee by mechanically stimulating relocated cutaneous tissues salvaged from the amputated limb or, alternatively, bioelectrically activating sensory nerve fibers in the residual limb using a novel neural interface design.

The surgical reconstruction methodology and implantable system of the invention significantly increases the potential for natural neural control of prostheses, such as artificial limbs and functional electrical stimulation devices. The system utilizes the neural activity within the residual biological limb generated in the peripheral nerves and/or the electromyographic activity generated through muscle tissue activation. Such nerve and muscle tissues may be native to the residual limb, or they may be relocated to the residual limb through a plurality of surgical manipulations. Such manipulations may include free muscle grafts or pedicle muscle graft

RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No. 17/120,938, filed Dec. 14, 2020, which is a continuation of U.S. application Ser. No. 15/233,241, filed Aug. 10, 2016, now U.S. Pat. No. 10,898,351, issued Jan. 26, 2021, which is a divisional of U.S. application Ser. No. 14/520,766, filed Oct. 22, 2014, now U.S. Pat. No. 9,474,634, issued Oct. 25, 2016, which claims the benefit of U.S. Provisional Application No. 61/894,040, filed on Oct. 22, 2013, and U.S. Provisional Application No. 62/019,266, filed on Jun. 30, 2014. The entire teachings of the above applications are incorporated herein by reference.

BACKGROUND OF THE INVENTION

Recent advances in prosthetic limbs include the provision of multiple degrees of freedom as well as powered actuators that have the potential to provide substantially greater functionality than the passive devices that existed just a decade ago. Despite these engineering accomplishments, developers still struggle with the issue of how to provide the prosthesis user with methods for coordinating the simultaneous control of all of the joints that are involved with, for example, object manipulation in the upper extremity case, or standing and walking in the lower extremity case. This deficit was first apparent for upper extremity prostheses, which now can provide elbow function, wrist rotation, and hand opening and closing. Today's commercially available, upper-extremity prosthetic controllers make use of the EMG activity (electro-myographic activity generated by muscle contraction) of functional native muscles that are present in the amputee's residual limb. This approach allows for proportional control with minimal execution delay. When the EMG activity used for prosthetic control arises from a pair of antagonistic muscles that would normally move the homologous biological joint (e.g., the biceps and triceps controlling flexion and extension, respectively, of the prosthesis elbow joint), the neurally controlled EMG commands are completely intuitive and thus easy to master.

However, more commonly in practice, the same set of EMG signal sources are used to control additional prosthetic joints, and this requires that the command sources be switched among the assigned joints in a serial manner. The resulting motion for most activities is thus awkward, time consuming, and tedious, since it breaks up any compound arm and hand movement into serial positioning steps, resulting in poor utilization of powered prostheses. In the lower extremity, powered ankle and knee joints are just becoming available to the general population. However, commercial lower-extremity prostheses typically do not utilize EMG as a source of control signals. Artificial sensory and computational systems have been demonstrated to provide some degree of control over ankle and knee flexion and extension for powered leg prostheses (E. C. Martinez-Villalpando and H. M. Herr, “Agonist-antagonist active knee prosthesis: A preliminary study in level-ground walking,” Journal of Rehabilitation Research & Development (JRRD), vol. 46, no. 3, pp. 361-73, 2009; S. Au, J. Weber, and H. M Herr, “Powered Ankle-Foot Prosthesis Improves Walking Metabolic Economy,” IEEE Transactions on Robotics, vol. 25, no. 1, pp. 51-66, 2009; H. M. Herr and A. M. Grabowski, “Bionic ankle-foot prosthesis normalizes walking gait for persons with leg amputation,” Proceedings of the Royal Society B, vol. 279, no. 1728, pp. 457-464, February 2012; E. J. Rouse, L. M. Mooney, E. C. Martinez-Villalpando, and H. M. Herr, “A clutchable series-elastic actuator: design of a robotic knee prosthesis for minimum energy consumption,” Proceedings of the IEEE International Conference on Rehabilitation Robotics, 2013). It is well appreciated, however, that the next generation of devices should provide smooth, simultaneous volitional-neural control over several degrees of freedom, such as the knee, ankle and subtalar joints. In that case, simultaneous control of several degrees of freedom will require multiple sources of independent, reliable, and intuitive control that can best be obtained by interfacing with the amputee's extrinsic neural control.

The efficacy of using an EMG-based neural activity approach for achieving simultaneous control of multiple prosthetic joints has been demonstrated in principle by a technique now referred to as “Targeted Muscle Re-innervation,” or TMR (T. A. Kuiken, G. A. Dumanian, R. D. Lipschutz, L. A. Miller, K. A. Stubblefield, “The use of targeted muscle reinnervation for improved myoelectric prosthesis control in a bilateral shoulder disarticulation amputee, Prosthetics and Orthotics International, vol. 28, pp. 245-53, 2004; T. A. Kuiken, “Targeted reinnervation for improved prosthetic function,” Physical Medicine and Rehabilitation Clinics of North America, vol. 17, no. 1, pp. 1-13, 2006). For transhumeral prosthetic control, for example, TMR utilizes the activity of all four of the arm trunk nerves. As a surgical procedure, each trunk nerve is mobilized from the brachial plexus, and each nerve is anastomosed to a separate division of the pectoralis major muscle of the chest. The nerves grow into and innervate their respective new muscle targets and can independently cause contractions of the respectively innervated pectoral muscle divisions. The four recorded muscle signals can then be assigned to prosthetic elbow, wrist, and hand functions according to the original natural hand control function of each of the translocated nerves. For example, hand closing is controlled by evoked EMG activity from the pectoral muscle division innervated by the median nerve, and hand opening is controlled by EMG activity from the muscle division innervated by the radial nerve. Essentially, the operator's brain performs the coordination of the prosthesis joints when a complex task is performed. Despite the laudable success of the original and ensuing demonstrations, the TMR approach has a few shortcomings; for instance, the native innervation of the pectoral muscle (or other selected host muscle) must be removed so that the normal activation of the host muscle by its native innervation does not interfere with that by the transferred nerves. Having to eliminate the functionality of any native tissue for the greater good is not optimal. There are also some limitations regarding how far away a given nerve can be moved in order to connect it to a suitable muscle target. Finally, the use of surface recorded EMG and contiguous muscle targets can lead to inconsistent signal amplitudes and objectionable channel crosstalk (T. A. Kuiken, M. M. Lowery, and N. S. Stoykov, “The effect of subcutaneous fat on myoelectric signal amplitude and cross-talk,” Prosthetics and Orthotics International, vol. 27, no. 1, pp. 48-54, 2003). This last issue has been addressed by using a large array of recording sites and performing substantial pattern recognition to interpret a user's intended movements unambiguously. Over time, however, it is still necessary to “re-tune” the system, which is a substantial inconvenience.

Therefore, there is a need for a method of reversing motor impairment of a human limb, and of restoring at least partial function of a human limb that overcomes or minimizes the above-referenced problems.

SUMMARY OF THE INVENTION

The invention generally is directed to a method of restoring at least partial function of a human limb, to reversing motor impairment of a human limb, to simulating proprioceptive sensory feedback from a device, and to simulate cutaneous sensory feedback from a device.

In one embodiment, the method of restoring at least a partial function of the human limb includes surgically removing from a surgical site at least a portion of an injured or diseased human limb from an individual, leaving intact at least one selected muscle from the damaged portion of the human limb, including at least one of blood vessels and nerves associated with that portion of the at least one selected muscle. The at least one selected muscle is transplanted into the remaining biological body of the individual and the at least one transplanted selected muscle, or associated nerve, is contacted with an electrode, whereby signals can be transmitted to and from at least one of the nerve and its associated transplanted muscle to thereby control a device linked to the electrode and extending from the surgical site, thereby restoring at least partial function of the human limb. Examples of suitable devices for use with the method of the invention include a prosthetic limb, an orthotic limb and an exoskeletal limb.

In a specific embodiment, and at least one patch of skin is dissected, wherein the patch of skin includes at least one nerve selected from the group consisting of an intact native sensory nerve and a new regenerative innervation nerve. The patch of skin is translocated onto a non-anatomical portion of the individual from which the limb was removed. The translocated patch is contacted with an external prosthetic socket of a prosthetic limb, the prosthetic socket including at least one component that provides mechanical stimulation to the translocated patch of skin. In another embodiment, that further includes the steps of contacting the nerve of the patch of skin with a nerve cuff, wherein the nerve cuff is linked to a controller. The nerve is selectively stimulated by actuating the nerve with the controller. In another embodiment, the nerve includes at least one sensory nerve selected from the group consisting of sural, saphenous, tibial, peroneal, median, ulnar, and radial nerves. In still one embodiment, contact in the nerves of the transplanted selected muscles with an electrode includes implanting electrode on the epimysium of the selected muscle or intramuscularly in the selected muscles.

In another embodiment, the method of reversing impairment of a human limb includes transecting a nerve associated with the impairment of the limb of an individual to thereby form proximal and distal ends of the transected nerve. The proximal and distal ends of the transected nerve are placed into proximal and distal ends of a microchannel array, thereby causing the nerve to regenerate through the microchannel array. Sensory afferent information of the regenerated nerve is recorded using sensing electrodes within a plurality of afferent microchannels of the microchannel array. Motor efferent information is stimulated to provide efferent motor stimulus to the nerve using stimulating electrodes within the plurality of efferent microchannels of the microchannel array. The stimulating electrodes are electrically connected to a motor controller of a device. The sensing electrodes are electrically connected a sensory controller of the device, wherein the sensor controller is linked to at least one sensor of the biological limb that detects application of at least one of position, velocity, acceleration, and force of the biological limb, and whereby the sensory controller transmits detection of the position, velocity, acceleration, and force of the biological limb to the motor controller, and whereby the motor controller applies electrical stimulation via the stimulating electrodes, thereby reversing impairments of the human limb.

In still another embodiment, the invention is directed to a method of restoring at least partial function of the human limb of an individual that includes dissecting at least one patch of skin from individual, translocating the patch of skin onto a non-anatomical portion of the individual, wherein the skin patch includes at least one nerve selected from the group consisting of an intact native nerve and a new regenerative innervation nerve, and contacting the translocated skin patch with an external device, the device including at least one component that provides mechanical stimulation to the translocated skin patch, thereby restoring at least partial function of the human limb.

In still another embodiment, the method of the invention includes reversing the impairment of an amputated limb, including inserting a distal end of at least one transected nerve of an amputated limb into a proximal end of a microchannel array, placing at least one member of the group consisting of skin and muscle end organ at the distal end of the microchannel array, thereby causing the nerve to regenerate through the microchannel array and to innervate the at least one end organ. Efferent motor information of the regenerated nerve is recorded using sensing electrodes within a plurality of afferent microchannels of the microchannel array. The regenerated nerve is stimulated with afferent sensory information using stimulating electrodes within a plurality of afferent microchannels of the microchannel array. The sensing electrodes are electrically connected to a motor controller of a device. The stimulating electrodes are electrically connected to a sensory controller of the device, wherein the motor controller is linked to at least one sensor of the device that detects application of at least one member selected from the group consisting of position, velocity, acceleration, and force of the device, and whereby the motor controller transmits detection of the position, velocity, acceleration, and force by applying electrical stimulation via the stimulating electrodes, thereby providing the individual with a sensation simulating sensory feedback from the device, and reversing impairment of the amputated limb.

In yet another embodiment of the invention, the method includes simulating proprioceptive sensory feedback from a device, including the steps of the mechanically linking at least one pair of agonist and antagonist muscles, wherein a nerve innervates each muscle. The at least one pair of agonist and antagonist muscles are supported with a support, whereby contraction of the agonist muscle of each pair will cause extension of the paired antagonist muscle. At least one electrode is implanted in at least one muscle of each pair, and the at least one electrode is electrically connected to a motor controller of the device, thereby stimulating proprioceptive sensory feedback from the device.

In another embodiment, the invention is a method for simulating cutaneous sensory feedback from the device, including steps of excising a skin segment from a biological body part of an individual, the skin segment including at least one of a native nerve and a regenerative nerve supply. The skin segment is linked to at least one muscle having a nerve supply. An electrode is implanted in the at least one muscle. The skin segment and actuator muscle are supported on a support. The at least one electrode is electrically connected to a sensory controller of a device, wherein the controller is linked to a sensor of the device that detects application of at least one of stress, strain, contact, pressure and sheer at the device, and whereby the controller transmits detection of the stress, strain, contact, pressure or sheer by contracting the actuator muscle within electrical stimulation via the electrode, thereby stretching the mechanoreceptor of the skin segment and providing the individual with a sensation stimulating cutaneous sensory feedback from the device.

This invention has many advantages. For example, Applicants' claimed invention provides a strategy for clinicians to follow when planning an amputation procedure so that the possibility to later obtain enhanced prosthetic control is maximized. Specifically, in the case of limb amputation, this strategy may include deriving multiple independent electrical signals, such as electromyographic signals, and neural recorded signals to command powered actuators within an external prosthesis. Further, artificial sensory information may be provided from the externally-controlled limb prosthesis back to the amputee by mechanically stimulating relocated cutaneous tissues salvaged from the amputated limb or, alternatively, bioelectrically activating sensory nerve fibers in the residual limb using a novel neural interface design.

The surgical reconstruction methodology and implantable system of the invention significantly increases the potential for natural neural control of prostheses, such as artificial limbs and functional electrical stimulation devices. The system utilizes the neural activity within the residual biological limb generated in the peripheral nerves and/or the electromyographic activity generated through muscle tissue activation. Such nerve and muscle tissues may be native to the residual limb, or they may be relocated to the residual limb through a plurality of surgical manipulations. Such manipulations may include free muscle grafts or pedicle muscle grafts, which may include intact attached nerves and/or vasculature. Additionally, the musculature could be derived from transplanted muscle precursor cells or cultured muscle tissue. For amputation limb patients, the system includes means to record one or multiple independent channels of neural motor activity that can control the various degrees of freedom present in advanced powered prosthetic limbs. Further, the method of the invention provides for the possibility of sensory information input from a controlled external prosthesis back into the nervous system. With regard to cutaneous sensory feedback, this can be by electrically activating sensory nerves through a nervecuff and/or microchannel array directly, or by applying mechanical stimulation to the native skin of the residual limb or other cutaneous tissue, such as fingertip skin, that has been relocated by a grafting procedure to the residual limb.

The invention also includes means to provide proprioceptive feedback to the amputee. This can be achieved through direct electrical activation of muscle and tendon afferent nerve fibers using the microchannel array. The invention also allows relocated antagonistic muscle pairs to mechanically interact with each other in a reciprocal push-pull fashion, just as would occur if the agonist/antagonist muscle pair were attached to the opposing sides of a joint. This approach allows the muscle proprioceptive endings that are intrinsic to those muscles to be activated by a normal stretch stimulus that occurs with intact muscles operating around the same joint.

The invention also has application in neural interface technology, such as for spinal cord lesion patients, stroke patients and other motor impairment disabilities, in that sensory information from the distal biological limb, or biological member, can be recorded from channels within an implanted microchannel array. Such signals can then be employed in an artificial feedback algorithm to then stimulate distal limb muscles through motor channels within the same microchannel array, or an alternate microchannel array.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing will be apparent from the following more particular description of example embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating embodiments of the present invention.

FIG. 1 is a schematic representation of surgical removal of a portion of an injured or diseased human limb, in outline, leaving intact a portion of selected muscles, including blood vessels and nerves associated with that portion of the selected muscles, according to one embodiment of the method of the invention.

FIG. 2 A is a schematic representation of transplantation of the selected muscles of FIG. 1 to a surgical site of the individual where the limb was removed according to the embodiment of the method of the invention of FIG. 1 .

FIG. 2 B is a schematic representation of implanting an electrode on to the epimesial surface of the selected muscles of FIG. 2 A .

FIG. 3 is a schematic representation of providing electrical isolation between relocated and native muscles.

FIG. 4 is a schematic representation of surgical removal of a portion of an injured or diseased human limb, in outline, leaving intact a portion of selected muscles and selected glabrous skin patches, including blood vessels and nerves associated with those portions of the selected muscles and glabrous skin patches, according to another embodiment of the invention.

FIG. 5 A is a schematic representation of grafting a patch of skin into the individual shown in FIG. 4 at the surgical site where the limb or limb portion was removed according to the embodiment of the invention of FIG. 4 .

FIG. 5 B is a cross section of the patch of skin grafted into the individual as shown in FIG. 5 A .

FIG. 6 A is a first representation of contacting a grafted patch of skin transplanted from finger pads of an individual with an external prosthetic socket of a prosthetic limb according to another method of the invention, wherein the prosthetic socket includes at least one actuator component that provides mechanical stimulation of the grafted patch of skin.

FIG. 6 B is a second, subsequent representation of contacting a grafted patch of skin transplanted from finger pads of an individual with an external prosthetic socket of a prosthetic limb according to another method of the invention, wherein the prosthetic socket includes at least one actuator component that provides mechanical stimulation of the grafted patch of skin.

FIG. 6 C is a schematic representation of a segment of the prosthetic and the actuator shown in FIG. 6 B .

FIG. 6 D is a schematic representation of the prosthetic of FIG. 6 C after actuation of the actuator.

FIG. 7 A is a schematic representation of contacting native sensory innervation of a skin patch with nerve cuffs, wherein the nerve cuffs are linked to a controller, and selectively stimulating the native sensory innervation by actuating the nerve cuffs with the controller, according to yet another embodiment of the invention.

FIG. 7 B is another schematic representation of the embodiment of the invention shown in FIG. 7 A , showing placement of implanted electronics and the nerve cuffs of FIG. 7 A .

FIG. 8 A is a schematic representation of transecting a nerve of a limb of an individual to thereby form proximal and distal ends of the transected nerve, and of placing the proximal and distal ends of the transected nerve in a microchannel array, the microchannel array including a bidirectional interface that records afferent information of the nerve and that provides efferent stimulus to the nerve, once the nerve has regenerated in the microchannel array, according to another embodiment of the method of the invention.

FIG. 8 B is a representation of one embodiment of placement of the microchannel array at the surgical site of an individual and relative location of a prosthetic limb controlled by the microchannel array.

FIG. 9 is a schematic representation of the microchannel array of FIGS. 8 A and 8 B , wherein nerve fibers from a nerve proximal to an amputation site grow through the array and connect to target tissue nerves arranged on the other side of the array.

FIG. 10 is a schematic representation of another embodiment of the microchannel array of FIGS. 8 A and 8 B , wherein nerve fascicles from a proximal nerve in the residual limb are separated by function and placed into different channels of the array, whereby the fascicles regenerate through the array and reconnect to the native innervation of appropriate target tissues that have been relocated and arranged on the other side of the array.

FIG. 11 A is a schematic representation of still another microchannel array employed by at least one embodiment of the method of the invention, wherein nerves in a paralyzed limb affected by a motor impairment disability (e.g., spinal cord lesion) are transected, and micro-channel array devices are placed between the proximal and distal nerve stumps whereby, after nerve regeneration, the limb may be controlled via artificial muscle stimulations using sensory recordings from channels within the implanted array devices.

FIG. 11 B is a representation of placement of the microchannel array of FIG. 11 A .

FIG. 12 is a schematic representation of one embodiment of a method for fabricating a three-dimensional array suitable for use by at least one embodiment of the method of the invention.

FIG. 13 A is an exploded view of one embodiment of a three-dimensional microchannel array suitable for use by at least one method of the invention.

FIG. 13 B is a perspective view of the assembled three-dimensional microchannel array of FIG. 13 A .

FIG. 14 is schematic representation of supporting at least one pair of agonist and antagonist muscles by one embodiment of the method of the invention, whereby contraction of the agonist muscle of each pair will cause extension of the paired antagonist muscle, and whereby the agonist-antagonist muscle pair provide proprioceptive information about movement and impedance via activity generated from the muscle spindle and tendon afferents of the agonist-antagonist muscle pair.

FIG. 15 is a schematic representation of a proprioceptive muscle Regenerative Peripheral Nerve Interface (Pro-m-RPNI) comprising an agonist-antagonist muscle pair series secured to bone or another biological structure at either end, suitable for employment in one embodiment of the method of the invention.

FIG. 16 a schematic representation of a linear Pro-m-RPNI in which the native tendon-bone junction at either end of the series is preserved to enable attachment to a synthetic structure.

FIG. 17 is a schematic representation of a Pro-m-RPNI secured about a synthetic spool shown comprising: 1) a synthetic spool; 2) an agonist muscle; 3) an agonist motor/afferent nerve; 4) an agonist electrode for electromyographic sensing and functional electrical stimulation; 5) agonist muscle spindle fibers; 6) an agonist Golgi tendon organ; 7) an antagonist muscle; 8) an antagonist motor/afferent nerve; and 9) an antagonist electrode for electromyographic sensing and functional electrical stimulation.

FIG. 18 is a schematic representation of a unidirectional Cutaneous Sensory RPNI (Cut-s-RPNI).

FIG. 19 is a schematic representation of a multi-directional Cut-s-RPNI around a synthetic sphere that is suitable for use in at least one method of the invention.

FIG. 20 is a schematic representation of a Pro-m-RPNI and a Cut-s-RPNI integrated with a bionic prosthesis.

DETAILED DESCRIPTION OF THE INVENTION

A description of example embodiments of the invention follows.

The invention generally is directed to a method of restoring at least partial function of a human limb, to reversing motor impairment of a human limb, to simulating a proprioceptive sensory organ for a human limb or organ, and to simulating a cutaneous sensor organ for a human limb or organ of an individual.

One goal of amputation surgery is to use the muscle tissues at the distal end of the residual limb to provide an appropriate cone shape to the limb so that a prosthetist will be able to fit a socket to the limb that will receive an artificial prosthesis. The distal ends of amputated nerves are usually buried into fat tissue or deep into the residual limb to provide protection to them from mechanical stimulation, which might otherwise cause painful sensations.

One critical innovation that is described herein is a strategy for clinicians to follow when planning an amputation procedure so that the possibility to later obtain enhanced prosthetic control is maximized. In the case of limb amputation, this strategy would include deriving multiple independent EMG signals and neural recorded signals to command powered actuators within an external prosthesis. A further innovation is to provide for artificial sensory information from the external controlled limb prosthesis back to the amputee by mechanically stimulating relocated cutaneous tissues salvaged from the amputated limb, or by electrically activating sensory nerve fibers in the residual limb using a novel neural interface design.

EMG Acquisition Using Skin Surface Electrodes

Myo-electric powered upper extremity prostheses have traditionally employed surface recording techniques to sense EMG activity. Typically, EMG signals are registered using small metal button-shaped electrodes that are mounted within the shell of the prosthesis socket so that they contact the skin overlying the muscles selected for the control tasks. Other electrode materials are possible, including conductive polymers, metal-impregnated woven fabrics, and carbon composites, for example.

To achieve an acceptable signal to noise ratio (SNR) and exclude unwanted biosignals, such as the electrocardiogram, a bi-polar recording configuration generally is recommended (C. J. De Luca, DelSys Inc. “Surface Electromyography: Detection and Recording,” DelSys Inc., Tutorial, 2002), although other configurations, such as a tri-polar recording, configuration could be employed.

It is also possible to cover an area of skin with an array of electrode elements and combine their outputs in arbitrary combinations in order to improve the SNR or to improve the ability to isolate the activity of individual muscles. Surface EMG acquisition has the advantage that it is non-invasive and the electrodes can be relocated if desired. There are, however, several disadvantages associated with surface recording. These include low signal amplitudes and variability in the signal amplitude caused by perspiration, changes in the thickness of the subcutaneous fat between the electrode and the underlying muscle, and movement of the electrodes relative to the recorded muscle from rotation of the limb and stretching of the skin. Other serious limitations of surface recording are contamination of the signal from activity in neighboring muscles and the inability to record selectively from muscles that are not superficial.

EMG Acquisition Using Implanted Sensors

The limitations imposed with surface recording of EMG activity can largely be mitigated by securing electrodes directly onto the epimesial surface of the muscle or by placing penetrating electrodes into the muscle tissue itself. Implantable epimesial electrodes and coiled wire intramuscular electrodes developed for electrical stimulation of muscle, but suitable for recording EMG activity, are known in the art. Variations of these designs could include bi-filar intramuscular coiled wire electrodes and epimesial electrodes, (P. A. Grandjean and J. T. Mortimer, “Recruitment properties of monopolar and bipolar epimysial electrodes,” Annals of Biomedical Engineering, vol. 14, no. 1, pp. 53-66, 1986), which contain additional contact sites attached to a common backing.

An example of a suitable implantable device that acquires EMG activity from residual limb muscles for the control of powered artificial limbs is the BION2™ powered artificial limb, developed by the Alfred Mann Foundation which consists of a ceramic cylinder approximately 3 mm dia.×15 mm long that can be installed into a muscle by loading it into the lumen of a hypodermic needle and then withdrawing the needle, leaving the sensor behind in the tissue. Each sensor is a stand-alone device capable of recording electrical activity by means of electrode contacts that are located at the ends of the cylinder. Each sensor is addressable so that its registered data can be telemetered to a central receiver terminal located in the shell of the prosthesis. Power for the implanted sensors is supplied via an RF link from a single transmitter coil that is located around the circumference of the prosthesis shell and communicates with all of the BION2™ devices that are implanted in the tissues that lie beneath the coiled region. An example application of these sensors is in an Implantable Myoelectric Sensor (IMES) System, described in R. F. Weir, P. R. Troyk, G. A. DeMichele, D. A. Kerns, J. F. Schorsch, and H. Maas, “Implantable myoelectric sensors (IMESs) for intramuscular electromyogram recording,” IEEE Transactions on Biomedical Engineering, vol. 56, no. 1, pp. 159-171, 2009.

Another implementation of an implantable EMG controller system includes a centralized processer package that resembles a “pacemaker” module. It has several paired leads that extend from the processor out to individual muscles. Each set of leads terminates in a set of button-shaped electrodes that are sutured to the epimesium of the muscles used to control the actuators of a powered prosthesis. More recently, a smaller device has been developed that includes an ASIC dedicated specifically for recording and transmitting EMG activity. (B. D. Farnsworth, Wireless Implantable EMG Sensing Microsystem, Masters thesis, Case Western Reserve University, August 2010).

Direct Interfacing to Peripheral Nerves

It has long been recognized that superior prosthetic limb control could be obtained if it was possible to establish the means to achieve a bi-directional interface with the peripheral nerves present in the residual limb. Researchers have applied several different approaches to achieve this goal, (K. Yashida and R. Riso, “Peripheral nerve recording electrodes and techniques,” in Neuroprostheses in Theory and Practice vol. 2, K. W. Horch and G. S. Dhillon, Eds. Hakensack, NJ: World Scientific, 2004, pp. 683-744), including various designs of circumferential nerve cuffs (e.g., Huntington Helix, W. F. Agnew, D. B. McCreery, T. G. H. Yuen, and L. A. Bullara, “Histologic and physiologic evaluation of electrically stimulated peripheral nerve: Considerations for the selection of parameters,” Annals of Biomedical Engineering, vol. 17, pp. 39-60, 1989); self sizing spiral cuffs (G. G. Naples, J. T. Mortimer, A. Scheiner, and J. D. Sweeney, “A spiral nerve cuff electrode for peripheral nerve stimulation,” IEEE Transactions on Biomedical Engineering, vol. 35, no. 11, pp. 905-916, 1988); multi-polar cuffs (C. Veraart, W. M. Grill, and J. T. Mortimer, “Selective control of muscle activation with a multipolar nerve cuff electrode,” IEEE Transactions on Biomedical Engineering, vol. 40, no. 7, pp. 640-653, 1993; M. Schuettler and T. Stieglitz, “18polar hybrid cuff electrodes for stimulation of peripheral nerves,” in Proceedings of the International Functional Electrical Stimulation Society, Aalborg, Denmark, pp. 265-268, 2000) and cuffs with multiple chambers, (J. A. Hoffer, Y. Chen, K. Strange, and P. R. Christensen, “Nerve cuff having one or more isolated chambers,” U.S. Pat. No 5,824,027 A, Oct. 20, 1998). Such “wrap around” cuffs designs have the inherent limitation that it is difficult to record from or to stimulate nerve fascicles that are not located on the surface of the nerve and that may lie deep within the trunk nerve. One cuff design acts to mitigate this problem by flattening and hence reshaping the nerve to force fascicles to align side by side, thereby providing more equal access to all fascicles of the nerve, (D. Tyler and D. Durand, “Flat interface nerve electrode and a method for use,” U.S. Pat. No. 6,456,866 B1, Sep. 24, 2002).

Penetrating Interfascicular Electrodes and Micro-electrode Arrays

Efforts to achieve better fiber specificity for recording and stimulation have led to the development of an array of needle-like electrodes (resembling a brush) having 100 contact points that is inserted transversely into the peripheral nerve. This approach allows nearly single unit specificity, similar to what is achieved using individual micro-electrodes. Despite this inherent advantage, thus far, electrode stability remains a major issue, because the electrode contact points tend to be extruded away from their original nerve fiber locations over time, (A. Branner and R. A. Normann, “A multielectrode array for intrafascicular recording and stimulation in sciatic nerve of cats,” Brain Research Bulletin, vol. 51, no. 4, pp. 293-306, 2000).

Another strategy to achieve high fiber specificity involves drawing fine wire or conductive polymer filaments into the nerve, essentially using a sewing technique for implantation. Each filament contains a small zone that is an electrode contact site and is capable of recording or stimulating nearby nerve fibers. Again, while this approach has shown the ability to isolate individual nerve fiber activity, over time the contact site moves relative to the nerve fibers, so that long term stability so far typically is not adequate for clinical use (M. S. Malagodi, K. W. Horch, and A. A. Schoenberg, “An intrafascicular electrode for recording of action potentials in peripheral nerves,” Annals of Biomedical Engineering, vol. 17, pp. 397-410, 1989; K. Yoshida and R. B. Stein, “Characterization of signals and noise rejection with bipolar longitudinal intrafascicular electrodes,” IEEE Transactions on Biomedical Engineering, vol. 46, no. 2, pp. 226-234, 1999; and S. M. Lawrence, J. O. Larsen, K. W. Horch, R. Riso, and T. Sinkjaer, “Long-term biocompatibility of implanted polymer-based intrafascicular electrodes,” Journal of Biomedical Materials Research, vol. 63, no. 5, pp. 501-506, 2002). Another severe limitation is that the number of fibers that can be “sewn” into a given nerve is very small (˜perhaps 10), and this can result in a very poor sampling of the potential information that is available in a peripheral nerve.

Regeneration-Based Nerve Interfaces

Regardless of advances made in cuff-based nerve interface designs, the extent of specificity that can be obtained for stimulating and recording is still extremely limited. Much better selectivity can be achieved if the fibers at the end of an amputated nerve are allowed to grow into a structure that consists of an array of micro-channels. Experience has shown that nerve fibers will invade each of the channels, and this effectively separates the nerve into small numbers of fibers that are likely to share some commonalities in function. Thus, a single micro-channel can include motor fibers that originally subserved a single muscle rather than multiple muscles. Similar benefits apply with regard to sensory nerve fibers, where the contents of a single micro-channel can include of sensory fibers that are of a single sensory modality, such as light touch or sustained pressure, or fibers that have receptive fields restricted to a small perceived locus on the phantom limb.

The development of regeneration electrodes began with “sieve” type designs that were disks with an array of fine caliber holes or slots drilled through them, (see, e.g., D. J. Edell, “A peripheral nerve information transducer for amputees: long-term multichannel recordings from rabbit peripheral nerves,” IEEE Transactions on Biomedical Engineering, vol. 33, no. 2, pp. 203-214, 1986; G. T. A. Kovacs, C. W. Storment, and J. M. Rosen, “Regeneration microelectrode array for peripheral nerve recording and stimulation,” IEEE Transactions on Biomedical Engineering, vol. 39, no. 9, pp. 893-902, 1992; R. M. Bradley, R. H. Smoke, T. Akin, and K. Najafi, “Functional regeneration of glossopharyngeal nerve through micromachined sieve electrode arrays,” Brain Research, vol. 594, no. 1, pp. 84-90, 1992; R. M. Bradley, X. Cao, T. Akin, and K. Najafi, “Long term chronic recordings from peripheral sensory fibers using a sieve electrode array,” Journal of Neuroscience Methods, vol. 73, no. 2, pp. 177-186, 1997; T. Akin, K. Najafi, R. H. Smoke, and R. M. Bradley, “A micromachined silicon sieve electrode for nerve regeneration applications,” IEEE Transactions on Biomedical Engineering, vol. 41, no. 4, pp. 305-313, 1994; Navarro, S. Calvet, F. J. Rodriguez, T. Stieglitz, C. Blau, M. Buti, E. Valderrama, and J. U. Meyer, “Stimulation and recording from regenerated peripheral nerves through polyimide sieve electrodes,” Journal of the Peripheral Nervous System, vol. 3, no. 2, pp. 91-101, 1998; L. Wallman, Y. Zhang, T. Laurell, and N. Danielsen, “The geometric design of micromachined silicon sieve electrodes influences functional nerve regeneration,” Biomaterials, vol. 22, no. 10, pp. 1187-93, 2001; and L. Wallman, A. Levinsson, J. Schouenborg, H. Holmberg, L. Montelius, N. Danielsen, and T. Laurell, “Perforated silicon nerve chips with doped registration electrodes: in vitro performance and in vivo operation,” IEEE Transactions on Biomedical Engineering, vol. 46, no. 9, pp. 1065-73, 1999). Such designs generally did not perform well because the electrode faces were located on the flat surfaces of the disks (perpendicular to the direction of nerve growth) and because the sharp edges of the holes could cut the nerve fibers that grew through the device. A more satisfactory design was a disk that was thick enough so that the electrode faces could be placed within lengthened holes, referred to as micro-channels. An example of early implementation of a micro-channel approach was in the MIT Biomechatronics Research Group, in collaboration with InnerSea Technology, where a bundle of 200 um ID polyimide tubing was sheared to a length of 3 mm to form a micro-channel array. Sharpened metal microelectrodes were introduced into the lumen of some of the channels so that neural recordings could be performed. The tibial nerve in a rabbit model was transected, and then the proximal nerve stump was allowed to grow into the implanted micro-channel array to form a reconnection to the distal nerve stump in a nerve-to-nerve repair. After recovery, it was demonstrated that neural activity could be recorded from the various array channels, and subsequent histological studies showed that the majority of the array channels contained regenerated nerve fibers and supporting vasculature (D. Edell, R. Riso, and H. Herr, “Bi-directional peripheral nerve interface for the control of powered prosthetic limbs,” DARPA Contract N66001-05-C-8030, 2006). Furthermore, in separate experiments using a “Y” maze paradigm, in which regenerating fibers were given a choice of growing into one of two chambers containing a small slice of either skin tissue or muscle tissue, it was shown that such “target tissues” are useful in trying to achieve a separation of motor efferent nerve fibers from sensory cutaneous afferent nerve fibers (D. Edell et al.). These studies were subsequently referenced as the basis for a patent submission that describes nerve regeneration based nerve interfacing (D. J. Edell and R. R. Riso, “Long term bi-directional axon-electronic communication system,” U.S. patent application Ser. No. 11/629,257, filed on Jun. 15, 2005 and published on Sep. 18, 2008 as U.S. 2008/0228240).

Subsequent developments of the micro-channel nerve interface strategy using a rat amputated nerve model in other laboratories (J. J. Fitzgerald, S. P. Lacour, S. B. McMahon, and J. W. Fawcett, “Microchannels as axonal amplifiers,” IEEE Transactions on Biomedical Engineering, vol. 55, no. 3, pp. 1136-1146, 2008; J. J. Fitzgerald, N. Lago, S. Benmerah, J. Serra, C. P. Watling, R. E. Cameron, E. Tarte, S. P. Lacour, S. B. McMahon, and J. W. Fawcett, “A regenerative microchannel neural interface for recording from and stimulating peripheral axons in vivo,” Journal of Neural Engineering, vol. 9, no. 1, pp. 016010, 2012; and S. P. Lacour, J. J. Fitzgerald, N. Lago, E. Tarte, S. McMahon, and J. Fawcett, “Long micro-channel electrode arrays: a novel type of regenerative peripheral nerve interface,” IEEE Transactions on Neural Systems and Rehabilitation Engineering, vol. 17, no. 5, pp. 454-60, 2009) have corroborated the hypothesis that a transected nerve will regenerate into a micro-channel structure and that electrodes placed within individual channels can record neural activity with minimal cross-talk (signal leakage) between channels.

FIRST EMBODIMENT

Description of Specific Embodiments of the Invention

FIGS. 1 , 2 A and 2 B are schematic representations of one embodiment of the method of the invention that includes the method of the restoring at least partial function of a human limb. At least a portion 10 (shown in outline) of an injured or diseased human limb 12 from an individual is surgically removed, leaving intact at least a portion of selected muscles 14 from the damaged portion of the human limb, including blood vessels and nerves 16 associated with that portion of the selected muscles 14 . The selected muscles are transplanted to a surgical site 18 of the individual where the human limb was removed. The transplanted selected muscles 14 and associated nerves 16 are then contacted with electrodes 20 ( FIGS. 2 A and 2 B ), whereby signals can be transmitted to and from nerves 16 at the transplanted muscles 14 to thereby control a prosthetic limb (not shown) that is linked to the electrodes and extends from the surgical site 18 .

A model for a transfemoral (above-the-knee) amputation is illustrated in FIG. 1 , but it will be clear to those of ordinary skill in the art that this embodiment is more broadly applicable to any amputation surgery in which muscles from the distal (amputated) limb can be salvaged with their native nerve innervation intact and perhaps, when possible, their native vasculature. For example, this embodiment could be applied to transhumeral, transradial, and transtibial amputation procedures. In such procedures, muscles can be relocated to the portion of the limb that is retained after the amputation surgery, providing new sources of signals, such as EMG signals, that can be harnessed for the control of advanced external devices, such as limb prostheses, orthoses or exoskeletons.

In a specific embodiment, using surface recording techniques, EMG signals from both the native and re-located muscles are sensed from electrodes mounted in the prosthetic socket shell, where electrodes contact the skin overlying the targeted muscles. Alternatively, an IMES implantable sensor, such as discussed earlier, is employed to measure and transmit the EMG signal from both native and re-located muscles within the residual biological limb post amputation surgery.

Listed below are examples of muscles that can be transferred to the residual limb during a transfemoral amputation surgical procedure in order to gain signals for the ankle and subtalar joint control of a prosthesis:

Tibialis anterior m.—ankle dorsiflexion and eversion

Gastronemius m.—ankle plantar flexion

Soleus m.—ankle plantar flexion

Posterior tibialis m.—ankle inversion

Peroneus Longus—eversion and plantar flexion of ankle

Additionally, this embodiment of the invention can be employed to control actuation of toes. This can be achieved by employing EMG command signals recorded from, for example, the following leg muscles:

Flexor Digitorum longus—2 nd toe flexor

Extensor Digitorum longus—2 nd toe extensor

Flexor Hallucis longus—great toe flexor

Extensor Hallucis longus—great toe extensor

In the case of a transfemoral amputation, surface recording electrodes

CLAIMS

Claims ( 20 )

What is claimed is:

1 . A method for providing cutaneous sensory feedback from a device, the method comprising:

excising a skin segment from a biological body part of an individual, the skin segment including at least one of a native nerve or a regenerative nerve supply; linking the skin segment with at least one muscle having a nerve supply; implanting an electrode in the at least one muscle; and electrically connecting the at least one electrode to a sensory controller of a device, wherein the controller is linked to a sensor of the device that detects application of at least one of stress, strain, contact, pressure or shear at the device, and whereby the controller transmits detection of the stress, strain, contact, pressure or shear by contracting the at least one muscle with an electrical stimulation via the electrode, thereby stretching a mechanoreceptor of the skin segment and providing the individual with a sensation simulating cutaneous sensory feedback from the device.

2 . The method of claim 1 , wherein the skin segment is an innervated portion of skin from a limb or a component of a limb.

3 . The method of claim 2 , wherein the muscle is an actuator muscle with a nerve supply.

4 . The method of claim 3 , wherein the device is a wearable device.

5 . The method of claim 4 , wherein the wearable device includes at least one member selected from the group consisting of a prosthesis, an orthosis and an exoskeleton.

6 . The method of claim 1 , wherein the innervating nerve includes at least one member selected from the group consisting of a regenerative nerve and a native nerve.

7 . The method of claim 1 , further comprising supporting the skin segment and the at least one muscle on a support.

8 . The method of claim 7 , wherein the skin is a strip of skin, and is attached to the at least one muscle at opposite ends of the strip, and wherein the support is a spool and the skin and the at least one muscle are supported about the periphery of the spool.

9 . The method of claim 7 , wherein the support is spherical and the skin segment is linked to two actuator muscles that, when contracted, provide tension to the skin segment in different directions, the at least one muscle being implanted with a separate stimulating electrode controlled independently by the controller.

10 . The method of claim 7 , wherein the support defines a surface shape that is non-spherical.

11 . The method of claim 1 , further including:

mechanically linking at least one pair of agonist and antagonist muscles, wherein a nerve innervates each muscle; supporting the at least one pair of agonist and antagonist muscles, whereby contraction of the agonist muscle of each pair will cause extension of the paired antagonist muscle; implanting at least one electrode in at least one muscle of each pair; and electrically connecting the at least one electrode to a motor controller of the device.

12 . The method of claim 11 , further including linking the motor controller and the sensory controller to a central controller that coordinates the efferent and afferent signals of the motor controller with afferent signals of the sensory controller.

13 . The method of claim 11 , wherein at least one of the innervated agonist and antagonist muscles includes at least one member selected from the group consisting of a Golgi tendon organ, muscle spindle stretch fibers, an efferent nerve fiber, and an afferent nerve fiber.

14 . The method of claim 13 , wherein at least one of the muscles includes a Golgi tendon organ and the other of the muscles includes spindle stretch fibers, wherein the Golgi tendon organs and the spindle stretch fibers generate afferent signals.

15 . The method of claim 11 , wherein the at least one electrode in at least one muscle of each pair senses muscle activation or causes muscle contraction via electrical stimulation.

16 . The method of claim 15 , wherein a position about a degree of freedom of the device can be sensed by an individual wearing the device, the agonist and antagonist muscles providing a proprioceptive sensory feedback to the individual.

17 . The method of claim 11 , wherein the device is a wearable device.

18 . The method of claim 17 , wherein the device includes at least one member selected from the group consisting of a prosthesis, an orthosis, and an exoskeleton.

19 . The method of claim 11 , wherein the nerve includes at least one member selected from the group consisting of a regenerative nerve and a native nerve.

20 . A method of restoring at least partial function of a human limb of an individual, comprising:

dissecting at least one patch of skin from the individual; translocating the patch of skin onto a non-anatomical portion of the individual, wherein the skin patch includes at least one nerve selected from the group consisting of an intact native nerve and a new regenerative innervation nerve; and contacting the translocated skin patch with an external device, the device including at least one component that provides mechanical stimulation to the translocated skin patch, thereby restoring at least partial function of the human limb.

US19/066,034

2013-10-22

2025-02-27

Peripheral Neural Interface Via Nerve Regeneration To Distal Tissues

Pending

US20250195243A1

( en )

Priority Applications (1)

Application Number

Priority Date

Filing Date

Title

US19/066,034

US20250195243A1

( en )

2013-10-22

2025-02-27

Peripheral Neural Interface Via Nerve Regeneration To Distal Tissues

Applications Claiming Priority (6)

Application Number

Priority Date

Filing Date

Title

US201361894040P

2013-10-22

2013-10-22

US201462019266P

2014-06-30

2014-06-30

US14/520,766

US9474634B2

( en )

2013-10-22

2014-10-22

Peripheral neural interface via nerve regeneration to distal tissues

US15/233,241

US10898351B2

( en )

2013-10-22

2016-08-10

Peripheral neural interface via nerve regeneration to distal tissues

US17/120,938

US12245956B2

( en )

2013-10-22

2020-12-14

Peripheral neural interface via nerve regeneration to distal tissues

US19/066,034

US20250195243A1

( en )

2013-10-22

2025-02-27

Peripheral Neural Interface Via Nerve Regeneration To Distal Tissues

Related Parent Applications (1)

Application Number

Title

Priority Date

Filing Date

US17/120,938

Division

US12245956B2

( en )

2013-10-22

2020-12-14

Peripheral neural interface via nerve regeneration to distal tissues

Publications (1)

Publication Number

Publication Date

US20250195243A1

true

US20250195243A1 ( en )

2025-06-19

Family

ID=51868332

Family Applications (4)

Application Number

Title

Priority Date

Filing Date

US14/520,766

Active

US9474634B2

( en )

2013-10-22

2014-10-22

Peripheral neural interface via nerve regeneration to distal tissues

US15/233,241

Active

US10898351B2

( en )

2013-10-22

2016-08-10

Peripheral neural interface via nerve regeneration to distal tissues

US17/120,938

Active

2034-11-27

US12245956B2

( en )

2013-10-22

2020-12-14

Peripheral neural interface via nerve regeneration to distal tissues

US19/066,034

Pending

US20250195243A1

( en )

2013-10-22

2025-02-27

Peripheral Neural Interface Via Nerve Regeneration To Distal Tissues

Family Applications Before (3)

Application Number

Title

Priority Date

Filing Date

US14/520,766

Active

US9474634B2

( en )

2013-10-22

2014-10-22

Peripheral neural interface via nerve regeneration to distal tissues

US15/233,241

Active

US10898351B2

( en )

2013-10-22

2016-08-10

Peripheral neural interface via nerve regeneration to distal tissues

US17/120,938

Active

2034-11-27

US12245956B2

( en )

2013-10-22

2020-12-14

Peripheral neural interface via nerve regeneration to distal tissues

Country Status (2)

Country

Link

US

( 4 )

US9474634B2

( en )

WO

( 1 )

WO2015061453A1

( en )

Families Citing this family (41)

* Cited by examiner, † Cited by third party

Publication number

Priority date

Publication date

Assignee

Title

ITPI20130004A1

( en )

*

2013-01-16

2014-07-17

Machinale S R L Fab

PROSTHETIC STRUCTURE FOR HAND AMPUTATION

US9585770B2

( en )

*

2013-03-15

2017-03-07

Michael T. McDonnell, JR.

Orthotic device for assisting limb movement

US11229789B2

( en )

2013-05-30

2022-01-25

Neurostim Oab, Inc.

Neuro activator with controller

JP2016523125A

( en )

2013-05-30

2016-08-08

グラハム エイチ． クリーシー

Local nervous stimulation

WO2015061453A1

( en )

2013-10-22

2015-04-30

Msssachusetts Institute Of Technology

Peripheral neural interface via nerve regeneration to distal tissues

JP6358427B2

( en )

*

2014-06-13

2018-07-18

国立大学法人 筑波大学

Wearable motion assist device

US10314725B2

( en )

2014-11-13

2019-06-11

The Regents Of The University Of Michigan

Method for amplifying signals from individual nerve fascicles

US11077301B2

( en )

2015-02-21

2021-08-03

NeurostimOAB, Inc.

Topical nerve stimulator and sensor for bladder control

US10166394B1

( en )

*

2015-10-15

2019-01-01

Hrl Laboratories, Llc

Device and method to automatically tune the nerve stimulation pattern of a sensory-feedback capable prosthesis

US10912346B1

( en )

2015-11-24

2021-02-09

Lockheed Martin Corporation

Exoskeleton boot and lower link

US11179251B2

( en )

2016-01-08

2021-11-23

Massachusetts Institute Of Technology

Method and system for providing proprioceptive feedback and functionality mitigating limb pathology

DE102016100886B4

( en )

*

2016-01-20

2017-12-21

Trutz Podschun

System for the regeneration of at least one severed nerve conduction

RU2627818C1

( en )

*

2016-03-15

2017-08-11

Сергей Игоревич Щукин

Method of bionic control of technical devices

US10675456B2

( en )

2016-09-20

2020-06-09

Robert Madeira

System and methods for percutaneous mechanical and/or neural interface

CA3073504A1

( en )

*

2017-08-30

2019-03-07

Lockheed Martin Corporation

Automatic sensor selection

US10953225B2

( en )

2017-11-07

2021-03-23

Neurostim Oab, Inc.

Non-invasive nerve activator with adaptive circuit

GB2565611B

( en )

*

2018-01-10

2019-08-07

Neuroloom Ltd

Bio-electronic interface

WO2019191239A1

( en )

*

2018-03-28

2019-10-03

Lockheed Martin Corporation

Lower-body exoskeleton using electromyography for direct force amplification

RU2712294C1

( en )

*

2019-03-13

2020-01-28

Федеральное государственное бюджетное военное образовательное учреждение высшего образования "Военно-медицинская академия имени С.М. Кирова" Министерства обороны Российской Федерации (ВМедА)

Method for accelerated recovery of innervation of distal extremity muscles in injuries of peripheral nerves in proximal segments

WO2020264214A1

( en )

2019-06-26

2020-12-30

Neurostim Technologies Llc

Non-invasive nerve activator with adaptive circuit

US11420053B2

( en )

*

2019-08-22

2022-08-23

Norbert Kaula

Diagnostic, neurostimulating, and therapeutic method applied to biological targets that are naturally integrated to each other

WO2021126921A1

( en )

2019-12-16

2021-06-24

Neurostim Solutions, Llc

Non-invasive nerve activator with boosted charge delivery

EP4093341A1

( en )

*

2020-01-23

2022-11-30

Massachusetts Institute of Technology

Mechanoneural interfaces for prosthetic control

KR20230024919A

( en )

2020-05-27

2023-02-21

더 존스 홉킨스 유니버시티

Systems and methods for implantable muscle interfaces

US20240225860A1

( en )

*

2021-05-03

2024-07-11

University Of Pittsburgh - Of The Commonwealth System Of Higher Education

Amplitude modulated high-frequency stimulation to elicit stochastic neural spiking activity

CN113713252B

( en )

*

2021-08-06

2023-11-10

重庆大学

Bionic proprioceptive reconstruction method for prosthetic wrist and elbow joints

CN118695826A

( en )

*

2021-09-19

2024-09-24

明尼苏达大学董事会

Artificial Intelligence Neuroprosthetic Hand

WO2023164202A1

( en )

*

2022-02-28

2023-08-31

The Regents Of The University Of Michigan

Systems and methods for controlling a prosthetic based on amplified nerve signals

US11833064B1

( en )

2022-06-03

2023-12-05

JSG IP Ventures, LLC

System and methods for residual limbs of amputees

US20260096766A1

( en )

*

2022-09-20

2026-04-09

The Cleveland Clinic Foundation

System and methods for treating neuropathologies of a subject

EP4633457A2

( en )

*

2022-12-15

2025-10-22

Massachusetts Institute of Technology

Fine wire muscle interfaces

US12426819B2

( en )

*

2022-12-28

2025-09-30

Korea Electronics Technology Institute

Multi-channel micro peripheral nerve sensor for neurosignal measurement

US20240225859A1

( en )

*

2023-01-10

2024-07-11

Kamil Podhola

Bionic limb system

CN115944332B

( en )

*

2023-01-12

2026-04-28

复旦大学附属华山医院

A Kraft electrode implantation device

KR20260018059A

( en )

*

2023-05-18

2026-02-06

더 리젠츠 오브 더 유니버시티 오브 미시건

Muscle cuff and skin regenerative peripheral nerve interface (RPNI) including intramuscular and intradermal electrodes

WO2025128813A1

( en )

*

2023-12-12

2025-06-19

President And Fellows Of Harvard College

Systems and methods for treatment of pain

US12329969B1

( en )

2024-08-20

2025-06-17

JSG IP Ventures, LLC

System and methods for residual limbs of amputees

US12337177B1

( en )

2024-08-20

2025-06-24

JSG IP Ventures, LLC

Method for residual limbs of amputees

US12558532B1

( en )

2024-08-20

2026-02-24

JSG IP Ventures, LLC

System and methods for modulating nerve activation

US12324754B1

( en )

2024-08-20

2025-06-10

JSG IP Ventures, LLC

System for residual limbs of amputees

US12558541B1

( en )

2024-08-20

2026-02-24

JSG IP Ventures, LLC

System and methods for residual limbs of amputees

Family Cites Families (32)

* Cited by examiner, † Cited by third party

Publication number

Priority date

Publication date

Assignee

Title

US3735425A

( en )

*

1971-02-10

1973-05-29

Us Of America The Secretary Of

Myoelectrically controlled prothesis

US4634422A

( en )

1984-05-31

1987-01-06

Adrian Kantrowitz

Percutaneous access device and method for implanting same

US4750499A

( en )

*

1986-08-20

1988-06-14

Hoffer Joaquin A

Closed-loop, implanted-sensor, functional electrical stimulation system for partial restoration of motor functions

US5158097A

( en )

*

1990-06-08

1992-10-27

Allegheny-Singer Research Institute

Paraneural stimulating lead

US5769875A

( en )

1994-09-06

1998-06-23

Case Western Reserve University

Functional neuromusclar stimulation system

US5824027A

( en )

1997-08-14

1998-10-20

Simon Fraser University

Nerve cuff having one or more isolated chambers

US6456866B1

( en )

1999-09-28

2002-09-24

Dustin Tyler

Flat interface nerve electrode and a method for use

ATE348646T1

( en )

*

2000-02-17

2007-01-15

Neurodan As

IMPLANTABLE SYSTEM FOR NEURAL MEASUREMENT AND NERVE STIMULATION

US6687538B1

( en )

2000-06-19

2004-02-03

Medtronic, Inc.

Trial neuro stimulator with lead diagnostics

WO2003033070A1

( en )

*

2001-10-16

2003-04-24

Case Western Reserve University

Neural prosthesis

US7396337B2

( en )

*

2002-11-21

2008-07-08

Massachusetts Institute Of Technology

Powered orthotic device

US7725175B2

( en )

*

2002-12-04

2010-05-25

Kinetic Muscles, Inc.

System and method for neuromuscular reeducation

KR20070061476A

( en )

*

2004-02-05

2007-06-13

모토리카 리미티드

Neuromuscular stimulation

WO2006009722A2

( en )

2004-06-17

2006-01-26

Innersea Technology, Inc.

Long term bi-directional axon-electronic communication system

JP4541867B2

( en )

*

2004-12-16

2010-09-08

本田技研工業株式会社

External force control method, external force control system, and external force control program

US20060189899A1

( en )

*

2005-01-10

2006-08-24

Flaherty J Christopher

Joint movement apparatus

US7233821B2

( en )

*

2005-03-31

2007-06-19

Medtronic, Inc.

Method and apparatus for evaluating ventricular performance during isovolumic contraction

US20070038311A1

( en )

*

2005-08-11

2007-02-15

Rehabilitation Institute Of Chicago

System and method for improving the functionality of prostheses

DE102006008501B3

( en )

*

2006-02-23

2007-10-25

Albert-Ludwigs-Universität Freiburg

Probe and method for data transfer between a brain and a data processing device

US8483820B2

( en )

2006-10-05

2013-07-09

Bioness Inc.

System and method for percutaneous delivery of electrical stimulation to a target body tissue

US7936337B2

( en )

2007-07-24

2011-05-03

Research In Motion Limited

Handheld electronic device and associated method enabling the output of non-alphabetic characters in a disambiguation environment

US20090292325A1

( en )

2008-05-02

2009-11-26

Cederna Paul S

Hybrid bioelectrical interface device

JP5676445B2

( en )

2008-08-01

2015-02-25

エヌディーアイ メディカル， エルエルシー

Portable assembly, system and method for providing functional or therapeutic neural stimulation

US20110257501A1

( en )

*

2010-04-19

2011-10-20

Katholieke Universiteit Leuven, K.U. Leuven R&D

Bio-Hybrid Implant for Connecting a Neural Interface With a Host Nervous System

WO2012097297A2

( en )

*

2011-01-14

2012-07-19

The Regents Of The University Of Michigan

Regenerative peripheral nerve interface

AU2012355384B2

( en )

*

2011-12-19

2017-03-16

Mainstay Medical Limited

Apparatus for rehabilitating a muscle and assessing progress of rehabilitation

KR101371359B1

( en )

*

2012-03-20

2014-03-19

한국과학기술연구원

Peripheral Nerve Interface System and Method for Prosthetic Hand Control

GB201205993D0

( en )

2012-04-03

2012-05-16

Ucl Business Plc

Control of prosthetic devices

US8999003B2

( en )

*

2012-08-31

2015-04-07

The Johns Hopkins University

Control system for prosthetic limb

CA2910346A1

( en )

*

2013-05-02

2014-11-06

Vanderbilt University

Coordinated control for an arm prosthesis

WO2015061453A1

( en )

2013-10-22

2015-04-30

Msssachusetts Institute Of Technology

Peripheral neural interface via nerve regeneration to distal tissues

US10376389B2

( en )

*

2016-11-01

2019-08-13

Glenn Gaston

Myoelectric prosthesis and method

2014

2014-10-22

WO

PCT/US2014/061773

patent/WO2015061453A1/en

not_active

Ceased

2014-10-22

US

US14/520,766

patent/US9474634B2/en

active

Active

2016

2016-08-10

US

US15/233,241

patent/US10898351B2/en

active

Active

2020

2020-12-14

US

US17/120,938

patent/US12245956B2/en

active

Active

2025

2025-02-27

US

US19/066,034

patent/US20250195243A1/en

active

Pending

Also Published As

Publication number

Publication date

US12245956B2

( en )

2025-03-11

US9474634B2

( en )

2016-10-25

US20210093470A1

( en )

2021-04-01

WO2015061453A1

( en )

2015-04-30

US20150173918A1

( en )

2015-06-25

US20160346099A1

( en )

2016-12-01

WO2015061453A8

( en )

2015-12-17

US10898351B2

( en )

2021-01-26

Similar Documents

Publication

Publication Date

Title

US12245956B2

( en )

2025-03-11

Peripheral neural interface via nerve regeneration to distal tissues

US20220031479A1

( en )

2022-02-03

Method And System For Providing Proprioceptive Feedback And Functionality Mitigating Limb Pathology

Raspopovic et al.

2021

Sensory feedback for limb prostheses in amputees

Ghafoor et al.

2017

Selectivity and longevity of peripheral-nerve and machine interfaces: a review

Del Valle et al.

2013

Interfaces with the peripheral nerve for the control of neuroprostheses

Dhillon et al.

2004

Residual function in peripheral nerve stumps of amputees: implications for neural control of artificial limbs

US10206793B2

( en )

2019-02-19

System and method for conscious sensory feedback

Navarro et al.

2005

A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems

Weber et al.

2007

Limb-state feedback from ensembles of simultaneously recorded dorsal root ganglion neurons

US20190117417A1

( en )

2019-04-25

Bidirectional limb neuro-prosthesis

Yoshida et al.

2017

Peripheral nerve recording electrodes and techniques

US20230050411A1

( en )

2023-02-16

Mechanoneural Interfaces for Prosthetic Control

US20080228240A1

( en )

2008-09-18

Long Term Bi-Directional Axon-Electronic Communication System

Dimante et al.

2020

Sensory feedback in upper limb prostheses

CN113713252A

( en )

2021-11-30

Bionic proprioception reconstruction method for wrist-elbow joint of artificial limb

Stieglitz et al.

2006

Biomedical microdevices for neural implants

Tian et al.

2024

Merging humans and neuroprosthetics through regenerative peripheral nerve interfaces

Haugland et al.

2000

Control with natural sensors

Li et al.

2005

Longitudinal intrafascicular electrodes in collection and analysis of sensory signals of the peripheral nerve in a feline model

Dhillon et al.

2004

Challenges to developing a neurally controlled upper limb prosthesis

Peripheral

2021

Advanced Control of Upper Extremity Prosthetic Devices

Horch et al.

2006

Towards a neuroprosthetic arm

Gozzi et al.

2023

Neural artificial encoding sensations of evoked by peripheral nerve stimulation for neuroprosthetic

Peresada et al.

2025

Artificial Hands

Wang et al.

2018

Decoding peripheral nerve sensory information with a spiked flexible neural interface

Legal Events

Date

Code

Title

Description

2025-03-11

STPP

Information on status: patent application and granting procedure in general

Free format text : DOCKETED NEW CASE - READY FOR EXAMINATION

2025-04-11

AS

Assignment

Owner name : MASSACHUSETTS INSTITUTE OF TECHNOLOGY, MASSACHUSETTS

Free format text : ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:HERR, HUGH M.;RISO, RONALD R.;SONG, KATHERINE W.;AND OTHERS;SIGNING DATES FROM 20141219 TO 20150306;REEL/FRAME:070815/0717

Related documents

• Generating augmented reality experiences utilizing physical objects to … — Meta Platforms Technologies, Llc (US20260037214A1)#653960
• Virtual reality system using multiple force arrays for a solver — DeepMotion, Inc. (US10657696B2)#653961
• Tracking position of device inside-out for virtual reality interactivity — Sony Interactive Entertainment America Llc (US10535153B2)#653962
• Augmented reality system with spatialized audio tied to user manipulated … — Magic Leap, Inc. (US11231770B2)#653963
• Big data-based autonomous flight drone system and autonomous flight method … — Rgblab Co., Ltd. (US20210390867A1)#653964