PROJECT SUMMARY We propose to develop a novel contact, label-free multimodality-based sensing probe that provides real-time intraoperative identification of nerves within the thermal damage threshold range of a surgical tool. The tool will facilitate prevention of direct/indirect nerve damage (termed iatrogenic nerve injury) during surgical procedures, as they are a major source of postsurgical complications, e.g., chronic pain. In the United States, chronic pain management is a major complicit factor in the ongoing opioid-related drug overdose epidemic. Annually, over 45 million surgical procedures are performed in the United States and an estimated 10% to 50% of them result in chronic postoperative pain patient outcomes. Though not every one of the at least 4.5 million chronic pain cases are definitively ascribable to iatrogenic nerve injury, it nonetheless represents a significant recurrent annual healthcare problem. Relatedly, analysis of large-scale nerve lesion treatment studies ascribes 25%, 60% and 94% respectively of sciatic, femoral and accessory nerve lesions addressed to iatrogenic nerve injury. Additionally, iatrogenic nerve injury features prominently in post-surgical quality of life issues that range from loss of sensation and motor function, to the aforementioned chronic pain, and morbidity. Reportedly, 2-3 years post radical prostatectomy ~60% of men are still impotent as a result of damaged cavernous nerves. Likewise, 20% - 60% of mastectomy breast cancer treatment survivors suffer chronic post-surgical pain that significantly reduces their quality of life, and injury to the intercostobrachial nerve is the primary cause. Even in surgeries with minimal neural damage risk like acoustic neuroma removal (<1%), spinal scoliosis surgery (<0.6%), and thyroidectomy (<2-3.8%) the consequences of nerve damage can be severe: leading to deafness, paraplegia, and even death respectively. The associated financial implications of iatrogenic nerve damage are significant. There are direct financial costs to the individual due to loss of employment and/or income, and to the healthcare industry as nerve damage is a common source of litigation with compensation being awarded in 82% of cases of spinal accessory nerve injury, for an example. The exposure of healthcare personnel and providers to medicolegal liability is extensive as Iatrogenic nerve injuries are commonly reported on the laryngeal nerve during thyroid operations, trigeminal nerve and inferior alveolar nerve during facial and oral surgeries, intercostal nerves during thoracic surgeries, and on the spinal accessory nerves, common peroneal nerve, superficial radial nerve, and genitofemoral nerve branches during various other surgeries. Consequently, as of 2015, medicolegal litigation risk was a primary driver for a $2.2 billion global market for intraoperative nerve monitoring projected to grow annually at 4.79% until 2025. Our proposed solution targets filling both the deficiencies of cu...