Since the introduction of shock wave lithotripsy (SWL) in the earlier 1980s by Domier Medical System, the technology of SWL has evolved significantly in terms of the means for shock wave generation, focusing, patient coupling, and stone location. However, the fundamental working principle of SWL remains unchanged despite of these technical developments. During this period, extensive basic research in shock wave physics and bio effects has also been carried out, mostly in academic research laboratories. In particular, the research in the past five years has begun to accumulate some critical insights regarding the mechanisms by which SWL works and how collateral tissue injury may be produced. Based on this knowledge, we have developed two novel SWL technologies that can be easily upgraded on a Dornier HM-3 lithotripter. For proof of principle, we have performed a series of in vitro and in vivo experiments that demonstrate the superiority of these technologies to the current gold standard - the Domier HM-3 lithotripter. The objective of this STTR proposal, therefore, is to translate these enabling technologies to the development of a next-generation commercial shock wave lithotripter for improved stone comminution with simultaneously reduced tissue injury. This task will be carried out through a synergistic collaboration between the Therapeutics Research Laboratory at Duke University and the HealthTronics Surgical Services, LLC (HTRN), a leading distributor of shock wave lithotripters. This project represents an unprecedented academic and industrial collaboration in the field of SWL and the proposed product should generate widespread impact and significant benefit to the clinical management of urolithiasis. In Phase I of this STTR proposal, our specific aim is to design and construction of a prototype shock wave generator based on in situ pulse superposition concept. Pressure waveform measurements and in vitro phantom studies will be performed to assess the stone fragmentation efficiency and propensity for vessel rupture produced by the prototype shock wave generator. Once the prototype with performance comparable to a HM-3 generator is constructed, a comprehensive investigation including animal studies with implanted artificial stones in porcine kidney will be performed in phase II to optimize the design of the proposed shock wave lithotripter system.