We propose to advance and clinically evaluate a multispectral Time-Resolved Fluorescence Spectroscopy (ms-TRFS) diagnostic technique as a tool for enhancing the functionality of the widely-used commercial da Vinci Surgical platform. This is a partnership between the University of California, Davis, which has pioneered intra-operative use of ms-TRFS and Intuitive Surgical, the global technology leader in minimally invasive robotic-assisted surgery. The ms-TRFS technique will provide label-free real-time (~secs) measures of biochemical and functional tissue features during robotic surgical procedures. We will integrate an optical port within the da Vinci instruments that when coupled to the ms-TRFS apparatus allows for both point- and imaging spectroscopy of tissue. The ms-TRFS parameters will provide surgeons with rapid clinical assessment of local pathologies, identification of tumor margins and other relevant tissues, and guidance of biopsy during robotic-assisted surgery. The initial clinical target of this proposal is intra-operative assessmen of head & neck cancer in patients undergoing TransOral Robotic Surgery (TORS). Incomplete surgical resection is strongly associated with tumor recurrence and the visible and palpable interface between normal and abnormal tissue is frequently subtle. As such it is particularly difficult and critical to accurately determine the boundary between tumor and normal tissue. We have extensive experience with both the fluorescence lifetime signatures of this cancer and clinically-compatible TRFS technology. The proposed work builds on our preliminary clinical data showing that TRFS can distinguish different types of tissues in the oral cavity including carcinoma. The proposed research strategy involves two steps: The first is to accelerate the clinical validation of a platform which will integrate the ms-TRFS device with the da Vinci Surgical Robot via a clinically available instrument, i.e. the Intuitive Surgical 5 French Introducer. This instrument includes a fiber optic port and will be initially used to provide direc measurements from various tissue types including cancer of the head & neck. This step will allow rapid generation of a database of optical features from different tissues types that can be used to determine the ms-TRFS diagnostic potential and represents a derisking step for the industry partner. The second is to develop a more specialized instrument including a port that can accommodate specific diagnostic needs during robot-assist surgical procedures. This will address our industrial partner's longer-term R&D programmatic goals and commercialization strategy. In summary, the proposed study addresses two critical challenges in robot-assisted head & neck surgery, i.e. the lack of tactile feedback and the inability to perform tissue diagnosis in real time during surgery; and has the potential to improve the surgeon's ability to perform complete surgical resection with low recurrence rates while preserving normal tissue and function. While the focus of this application is on TORS, we note the proposed technique can be broadly applied as the da Vinci Robot is used in a range of tumor surgeries including urologic, colorectal, gynecologic, and thoracic cancers.