* PROPOSALS ACCEPTED: Phase I and DP2 (Direct to Phase II). Please see the 15.3 DoD Program Solicitation and the DARPA 15.3 Phase I Instructions for Phase I requirements and proposal instructions.*
TECHNOLOGY AREA(S): Biomedical, Sensors
OBJECTIVE: Develop and demonstrate clinically-viable bio-interface technologies that have mechanical properties similar to tissue, yet can interface with conventional benchtop and/or implantable electronics to form complete systems for biological sensing and modulation. Areas of interest include implantable interface technologies for neural and other biological tissue, as well as wearable biosensors and interfaces.
DESCRIPTION: There is a critical need for DoD capabilities that would provide breakthrough medical treatments for wounded warriors with post-traumatic stress disorder (PTSD), anxiety, immune system dysfunction and other DoD-relevant health issues. Regulation of neural and other biological functions via interface technologies has become increasingly enticing as a means of clinical treatment. For instance, over the past several decades we have seen the emergence of neural recording and stimulation to restore sensorimotor capability and vagal nerve stimulation technologies for the treatment of epilepsy and depression. While these treatments have achieved moderate success, existing clinically approved technologies offer limited stability and precision, which significantly hinders their clinical translation. Despite recent noteworthy advancements in pre-clinical electrode technologies, existing devices suffer from reliability problems, often associated with tissue damage and/or mechanical failure of the device.
Even state-of-the-art interface technologies exert high mechanical strain on surrounding tissues, leading to scarring, persistent bleeding and neuronal damage. Tissue in the peripheral nervous system (PNS) has Young’s Modulus of approximately 600 kPa. Traditional electrodes are manufactured using either fine metal wires, such as platinum (168 GPa), or microfabricated from silicon (180 GPa). This six order of magnitude difference in stiffness leads to a number of issues—including tissue damage, surgical attachment and relative motion—which reduce the clinical viability of these technologies. By developing bio-interfaces with kPa-scale stiffness, it would be possible to attach neuromodulation devices to the PNS without incurring these problems. Proposed implantable neural interface devices should be able to penetrate the tough epineurium of a specified nerve (e.g. vagus, ulnar), enter multiple fascicles and accommodate the range of motion that the nerve typically encounters. Wearable technologies should similarly match the mechanical properties of skin and tissue to provide robust, biocompatible solutions for biological interfacing.
This topic seeks to advance the clinical readiness of bio-interface technologies by decreasing the biomechanical mismatch between manufactured devices and biological tissue. The most established approaches in this space use polymeric substrates with embedded conductors. There have been recent advances in materials that may push the Young’s Modulus down even further, such as shape memory polymers that soften when inserted into tissue. While these advances are important, all still use substrate materials that have a modulus greater than 10 MPa. Some early demonstrations of biologic materials such as collagen have yielded crude but functional devices with kPascale stiffness properties. Dissolvable carrier substrates have also shown promising results, but depend heavily upon the dissolution rate of the sacrificial material and leave behind tiny but stiff electrodes.
Despite these advances in materials science and device fabrication, there has been little progress towards demonstration of functional devices, much less mechanical testing with ex vivo nerve tissue or in vivo electrophysiological validation. Without this validation, promising new technologies will not be adopted by the neural interface community or medical device manufacturers.
PHASE I: Proposals to this topic should aim to develop and/or demonstrate mechanically compliant yet reliable biological interface devices that are wearable or implantable, enabling direct monitoring or modulation of biological signals in peripheral nerves and organs. Implantable PNS-specific devices should demonstrate an ability to penetrate the epineurium and perineurium of a nerve to insert kPa-scale electrodes into individual fascicles, and to do so at a scale and precision relevant to neuromodulation therapies. These devices should include interconnects to mate with standard benchtop or implantable electrophysiology equipment. Wearable devices should provide reliable measurement of biological signals that are relevant to quantifying health physiology.
Phase I deliverables include: Proof of concept demonstrating the feasibility of manufacturing and implementing novel soft bio-interface devices. Feasibility may be demonstrated through a variety of models, including tissue phantoms, in vitro, ex vivo, or in vivo studies. The final report must include a quantitative analysis of interface properties and mechanical characteristics. The final report should also contain detailed plans for Phase II.
PHASE II: Work in this SBIR topic should focus upon creating fully functioning interface devices suitable for chronic implantation in vivo. Performers should develop manufacturing and testing procedures to produce and verify the flexible bio-interface assembly. Devices should comprise a set of interconnects, flexible tethering leads and a compliant substrate containing a multitude of interface sites for stimulating and/or sensing neural activity (at fascicular resolution or better) or measuring biomolecules in vivo. The interface assemblies must be safe, effective and chronically stable for long-term use in animals or humans.
Phase II deliverables include: Demonstrate the reliability and scalability of the manufacturing approach. Proposals should include plans to develop and demonstrate individual compliant devices using batch manufacturing process flows capable of producing hundreds of identical devices. Studies should characterize the morphological and physiological properties of relevant tissue to develop advanced finite element models and validate these against ex vivo experiments with the soft interface technology. Phase II efforts must also demonstrate the lifetime of the devices through Failure Mode and Effects Analysis (FMEA), including mechanical, soak and electrical testing. Finally, the devices must be tested chronically in animal models to validate sensing and modulation capability, as well as cross-talk, impedance and other relevant properties. Tissue samples must undergo histological examination to demonstrate the extent of damage incurred during application or surgical insertion as well as after chronic use.
DIRECT TO PHASE II: Existing technologies that target peripheral nerves and have demonstrated capabilities are eligible for Direct to Phase II applications.
PHASE III DUAL USE APPLICATIONS: Highly effective clinical therapies for treating disease and mental health through biocompatible neuromodulation devices. Highly effective treatments for PTSD, anxiety, immune function, and other DoD-relevant health issues through biocompatible neuromodulation devices.
KEYWORDS: biology, neuroscience, peripheral nervous system, spinal cord, neuromodulation, nerves, shape memory polymers, silicone, electrode, collagen, elastomer.