SBIR-STTR Award

This SBIR Fast-track finalizes, tests, and commercializes the Acoustic Implant Protection (AIP) system, which uses the application of precision acoustic fields to penetrating neural implants to prevent electrode impedance rise and improve implant longevity. This submission is in response to: Notice of Special Interest (NOSI): NOT- MH-21-125 Translation of BRAIN Initiative Technologies to the Marketplace. Problem to be solved: Chronic neural implants hold great potential for illuminating features of neural function, treating neurological disorders, and enabling the next generation of brain-machine interface-based neuroprosthetics. Penetrating microelectrode arrays provide direct access to neural signals with high temporospatial resolution. However, their preclinical and clinical viability are limited by their poor longevity and variability in functionality due to the immune response or foreign body response (FBR). The FBR can cause glial scarring and neural cell loss near the electrode sites of penetrating arrays over a period of several weeks, which are leading causes of signal recording losses through both electrical isolation and spatial distancing effects. The FBR begins with electrode insertion, when damage to the blood brain barrier activates astrocytes and microglia. Although "˜soft' electrode materials, thinner shanks, and floating arrays have been developed to minimize the mismatch between brain and implant, none of these have demonstrated sufficient recording life and immunity to the FBR. Exogenous chemical means have been used to directly suppress the FBR, and have yielded positive results to varying degrees, but limitations of effectiveness, high costs, and/or undesirable side-effects still exist. A simple approach is needed to mitigate FBR for both preclinical and clinical use. Solution: Sub-threshold therapeutic ultrasound has recently been shown to have protective and healing effects in models of cerebral disease and injury, through promotion of neurotrophic factors. AMI successfully leveraged this principle in an R21 study evaluating low-intensity pulsed ultrasound (LIPUS) to mitigate the microglia response and improve longevity of neural interfaces. Product: This Fast-track delivers an AIP system for preclinical use with a reusable (releasable) annular transducer that delivers LIPUS to produce a neuro-protective environment around implanted microelectrodes. Phase I: Aim 1 - Electronics/System Adaptation for Preclinical Study. Aim 2 - Confirm ultrasound parameters for AIP annulus that safely stimulate cortical tissues comparable to Alpha design from R21. Phase I to Phase II Go-no-go. Portable, reusable AIP prototype produces measurable improvement in neural signal longevity over 6 weeks in preclinical microelectrode study. Positive feedback from potential end users. Aim 3- Integrate End User Design Feedback and Conduct Verification and Validation. Aim 4 - Optimize stimulation intervals for neural interface performance (SNR, unit detection) and demonstrate additional neuro- protective effects (glial cell activation, E-I balance) of LIPUS in preclinical studies.

Public Health Relevance Statement:


Project narrative:
Relevance - Penetrating electrode arrays can provide direct access to neural signals across the central and peripheral nervous system with high spatial resolution. Chronic electrode implants could revolutionize treatment for a range of medical conditions, including prosthetic motor control for amputees, and brain- machine interfacing for paraplegics. Unfortunately, device implantation causes an immune response that contributes to device failure over time. This project commercializes a device that uses acoustic fields to mitigate the immune response effects that cause electrodes to fail over time.

Project Terms:
Acoustics; Acoustic; Amputees; Anti-Inflammatory Agents; Anti-Inflammatories; Anti-inflammatory; Antiinflammatories; Antiinflammatory Agents; antiinflammatory; Astrocytes; Astrocytus; Astroglia; astrocytic glia; Blood - brain barrier anatomy; Blood-Brain Barrier; Hemato-Encephalic Barrier; bloodbrain barrier; Brain; Brain Nervous System; Encephalon; cell motility; Cell Locomotion; Cell Migration; Cell Movement; Cellular Migration; Cellular Motility; Motility; Chondroitin ABC Lyase; Chondroitinase ABC; Cicatrix; Scars; Dexamethasone; Disease; Disorder; Electrodes; Implanted Electrodes; Electronics; electronic device; Electrophysiology (science); Electrophysiology; Neurophysiology / Electrophysiology; electrophysiological; Environment; Enzymes; Enzyme Gene; Equilibrium; balance; balance function; Feedback; Foreign Bodies; Future; Goals; Head; Human; Modern Man; Immunity; Incidence; Inflammation; Laboratory Research; Longevity; Length of Life; life span; lifespan; Microelectrodes; Miniaturized Electrodes; Nervous System Diseases; Neurologic Disorders; Neurological Disorders; neurological disease; nervous system disorder; Nerve Cells; Nerve Unit; Neural Cell; Neurocyte; neuronal; Neurons; Noise; Oligodendrocytes; Oligodendrocytus; Oligodendroglia Cell; Oligodendroglia; Legs Paralysis; Lower Extremities Paralysis; Lower Limbs Paralysis; paraplegic; Paraplegia; Pathology; Common Rat Strains; Rat; Rats Mammals; Rattus; Research; Investigators; Researchers; Research Personnel; Risk; Rodentia; Rodents Mammals; Rodent; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Signal Transduction; Technology; Temperature; Testing; Time; Tissues; Body Tissues; Transducers; Translating; Translations; Equipment Malfunction; Device Failures; neurotrophic factor; neurotrophin; neutrophin; electric impedance; Electrical Impedance; Impedance; Prosthesis; Prosthetic device; Prosthetics; Injury; injuries; base; improved; Site; Chronic; Clinical; Phase; Medical; Microglia; Hortega cell; gitter cell; mesoglia; microglial cell; microgliocyte; perivascular glial cell; Peripheral Nervous System; Chemicals; Failure; Individual; cerebral; Cerebrum; Immunological response; host response; immune system response; immunoresponse; Immune response; Therapeutic; Morphology; tool; Life; mechanical; Mechanics; Pulse; Physiologic pulse; System; Degenerative Neurologic Diseases; Degenerative Neurologic Disorders; Nervous System Degenerative Diseases; Neural Degenerative Diseases; Neural degenerative Disorders; Neurodegenerative Diseases; Neurologic Degenerative Conditions; degenerative diseases of motor and sensory neurons; degenerative neurological diseases; neurodegenerative illness; Neurodegenerative Disorders; interest; Performance; neural; relating to nervous system; neuro-prosthetic; neuroprosthetic; neuroprosthesis; Nerve Impulse Transmission; Nerve Transmission; Neuronal Transmission; axon signaling; axon-glial signaling; axonal signaling; glia signaling; glial signaling; nerve signaling; neural signaling; neuronal signaling; neurotransmission; Devices; neural function; Neurophysiology - biologic function; Modeling; response; miniaturize; portability; Inflammatory Response; Effectiveness; preventing; prevent; Detection; Measurable; Preclinical Models; Pre-Clinical Model; Resolution; Exploratory/Developmental Grant; R21 Mechanism; R21 Program; exploratory developmental study; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Monitor; Development; developmental; Pathway interactions; pathway; pre-clinical; preclinical; preclinical study; pre-clinical study; cost; healing; design; designing; next generation; Outcome; brain computer interface; brain machine interface; Population; neuromechanism; neural mechanism; innovation; innovate; innovative; Impairment; pre-clinical research; preclinical research; clinical application; clinical applicability; Implant; implantation; prototype; commercialization; motor control; verification and validation; BRAIN initiative; Brain Research through Advancing Innovative Neurotechnologies initiative; glial activation; glial cell activation; human model; model of human; neural implant; brain implant; side effect; ultrasound

This SBIR Fast-track finalizes, tests, and commercializes the Acoustic Implant Protection (AIP) system, which uses the application of precision acoustic fields to penetrating neural implants to prevent electrode impedance rise and improve implant longevity. This submission is in response to: Notice of Special Interest (NOSI): NOT- MH-21-125 Translation of BRAIN Initiative Technologies to the Marketplace. Problem to be solved: Chronic neural implants hold great potential for illuminating features of neural function, treating neurological disorders, and enabling the next generation of brain-machine interface-based neuroprosthetics. Penetrating microelectrode arrays provide direct access to neural signals with high temporospatial resolution. However, their preclinical and clinical viability are limited by their poor longevity and variability in functionality due to the immune response or foreign body response (FBR). The FBR can cause glial scarring and neural cell loss near the electrode sites of penetrating arrays over a period of several weeks, which are leading causes of signal recording losses through both electrical isolation and spatial distancing effects. The FBR begins with electrode insertion, when damage to the blood brain barrier activates astrocytes and microglia. Although "˜soft' electrode materials, thinner shanks, and floating arrays have been developed to minimize the mismatch between brain and implant, none of these have demonstrated sufficient recording life and immunity to the FBR. Exogenous chemical means have been used to directly suppress the FBR, and have yielded positive results to varying degrees, but limitations of effectiveness, high costs, and/or undesirable side-effects still exist. A simple approach is needed to mitigate FBR for both preclinical and clinical use. Solution: Sub-threshold therapeutic ultrasound has recently been shown to have protective and healing effects in models of cerebral disease and injury, through promotion of neurotrophic factors. AMI successfully leveraged this principle in an R21 study evaluating low-intensity pulsed ultrasound (LIPUS) to mitigate the microglia response and improve longevity of neural interfaces. Product: This Fast-track delivers an AIP system for preclinical use with a reusable (releasable) annular transducer that delivers LIPUS to produce a neuro-protective environment around implanted microelectrodes. Phase I: Aim 1 - Electronics/System Adaptation for Preclinical Study. Aim 2 - Confirm ultrasound parameters for AIP annulus that safely stimulate cortical tissues comparable to Alpha design from R21. Phase I to Phase II Go-no-go. Portable, reusable AIP prototype produces measurable improvement in neural signal longevity over 6 weeks in preclinical microelectrode study. Positive feedback from potential end users. Aim 3- Integrate End User Design Feedback and Conduct Verification and Validation. Aim 4 - Optimize stimulation intervals for neural interface performance (SNR, unit detection) and demonstrate additional neuro- protective effects (glial cell activation, E-I balance) of LIPUS in preclinical studies.

Public Health Relevance Statement:


Project narrative:
Relevance - Penetrating electrode arrays can provide direct access to neural signals across the central and peripheral nervous system with high spatial resolution. Chronic electrode implants could revolutionize treatment for a range of medical conditions, including prosthetic motor control for amputees, and brain- machine interfacing for paraplegics. Unfortunately, device implantation causes an immune response that contributes to device failure over time. This project commercializes a device that uses acoustic fields to mitigate the immune response effects that cause electrodes to fail over time.

Project Terms: