The proposed Phase II SBIR project will develop a unique motor unit (MU) based control system (MU Drive™) that uses neural firings measured noninvasively and in real-time to drive an upper-limb prosthesis. Our Phase I effort successfully proved the technical merit and feasibility by demonstrating that MU firings can be measured from surface myoelectric recordings in real-time and used to provide a proportional control signal that substantially improves upon present amplitude-based methods for myoelectric control. In Phase II we will collaborate with leading experts across prosthetic service providers to advance our proof-of-concept into a functioning prototype control system that, when tested with state-of-the-art prosthetic hands, delivers simultaneous, coordinated control of the wrist, hand and fingers in 4 degrees-of-freedom; and in a manner that is responsive, precise and proportionally related to the intended effort. The research and development strategy will target three aims: 1) improve the MU Drive™ algorithms for simultaneous, coordinated, multi-degree-of- freedom control; 2) develop and integrate the MU Drive™ sensor/microcontroller system for use in a prosthetic socket; and 3) evaluate the MU Drive™ control system under use-case scenarios. The MU Drive™ algorithms will be enhanced to provide coordinated control of at least 4 degrees-of-freedom (by directly mapping patterns of MU firing behavior to functional prosthetic movements), repeatable functionality (by implementing adaptive MU tracking algorithms), and responsive performance (by reducing the processing time to minimize the overall delay). A new MU Drive™ sensor/microcontroller system will be developed for use within a prosthetic socket by designing replaceable contact-embedded silicone electrode interfaces, implementing biocompatible semi-conductive sensor encapsulation, and packaging a multi-level miniature DSP microcontroller to support on-board MU Drive™ control algorithms. The prototype MU Drive™ control system will be initially tested among trans-radial amputee subjects while controlling a table-top prosthesis (n=15) to evaluate the motion selection time, completion time, smoothness, and completion rate among other performance metrics relative to standard myoelectric interfaces. The final MU Drive™ control system will be fully-integrated into a body-worn prosthesis fitted to (n=5) trans-radial amputees and evaluated during use- case scenarios using a battery of functional tests including: Box and Blocks Test (BBT), Southampton Hand Assessment Procedure (SHAP), Assessment of Capacity for Myoelectric Control (ACMC) and the Orthotics and Prosthetics User Survey - Upper Extremity Functional Status (OPUS-UEFS). The deliverable MU Drive™ control system will be designed with full-compatibility with the current prosthetist-directed model of procurement, current insurance reimbursement policies and with existing state-of-the-art prosthesis technology to provide immediate broad-based...