PROJECT SUMMARY/ABSTRACT This application is for the NIBIB C3i Accell program. The objective of our parent R01 application (R01EB030102, Project Period: 08/01/2020–04/30/2024) is to perform small animal and large animal studies to obtain compelling preclinical evidence needed to support future clinical translation of focused ultrasound-enabled liquid biopsy (sonobiopsy). Through learnings from NIBIB’s C3i programs, we identified that one key risk toward commercialization of our technique is the need to optimize the design of the sonobiopsy device for clinical use and validated its feasibility and safety in biomarker release. The objective of our proposed research for the C3i Accell program is to address this key technical risk. Successful completion of this work will obtain data that will support our start-up company’s NIH SBIR/STTR grant application to further commercial development efforts.