TRAUMAS: Treatment and recovery augmented with electrical and ultrasound- mediated actuation and sensing

• Subtask 1.1.1. Development of piezoelectric array on flexible package for B-mode imaging and FUS. We will create a 64 × 64 array of ceramic piezoelectric elements (PZT or PMT) on to a flexible polyimide package at a pitch of , suitable for mouse model studies. The package itself with be fabricated by us in our cleanroom facilities or at a vendor, depending on available design rules for vendor manufacturing. This design will be scalable to larger arrays for use in human studies. Start-end date (Performer): Month 1/4 (Shepard, Rogers, Chitnis) • Subtask 1.1.2. Development of electrode array on flexible package for electrical stimulation with temporal interference. The same flexible package developed in Subtask 1.1.1 will incorporate electrodes to enable electrical stimulation through temporal interference (TI). Start-end date (Performer): Month 1/4 (Shepard, Rogers, Boyden) • Subtask 1.1.3. Development of electrochemical sensing capabilities on electrode arrays for metabolites, proteins, and pH through enzyme coating. We will seek to measure pH and at least three metabolites or proteins associated with the inflammatory or proliferation phases of wound healing. The use of enzyme coatings here is enabled by the fact that the active bandage can be replaced when it fouls or the enzymes degrade. Start-end date (Performer): Month 1/4 (Shepard, Rogers) • Subtask 1.1.6. Co-integration of ultrasound, electrical stimulation, and electrochemical analysis into a single patch device on a flexible package. This subtask will incorporate all of the elements developed in Subtasks 1.1.1 through 1.1.5. The flexible package will support both a wired (for testing) and wireless (battery-powered) interface. Start-end date (Performer): Month 5/9 (Shepard, Boyden, Rogers, Chitnis) • Subtask 1.1.9. Complete in vitro of electrochemical sensing from the TRAUMAS patch. We will demonstrate the ability to measure pH and at least three relevant metabolites or proteins through electrochemical detection at the TRAUMAS bandage. Start-end date (Performer): Month 11/15 (Rogers, Shepard) • Subtask 1.4.4. Postprocessing, packaging, and integration of the ASIC for the active scaffold. This will probably use similar interconnection approaches to those used for connecting the flexible CMOS chips to the flexible substrate in the bandage in Subtask 1.1.5. Start-end date (Performer): Month 6/9 (Rogers, Shepard, Lu, Hung) • Subtask 1.5.5. Collection of pH, temperature, and electrochemical sensor data from the TRAUMAS patch. This software will be tested and developed along with Subtask 1.1.9. Start-end date (Performer): Month 11/15 (Shepard, Rogers) OPTION PERIOD (PHASE II) • Subtask 2.1.1. Continued development of the TRAUMAS patch device for sensing and imaging. Start-end date (Performer): Months 25/48 (Shepard, Rogers, Chitnis) • Subtask 2.1.2. Continued development of the TRAUMAS patch device for actuation. Start-end date (Performer): Months 25/48 (Shepard, Rogers, Boyden, Chitnis)