SBIR-STTR Award

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is to develop a safer alternative to gallbladder surgery for elderly patients at higher risks of complications due to the effects of general anesthesia. Approximately 200,000 Medicare patients undergo surgery to remove their gallbladders every year. Unfortunately, 24% of these patients will experience a perioperative complication due to the effects of general anesthesia, totaling $500 M in cost annually to the US healthcare system. As the population ages and management of chronic disease improves, the need for alternatives to gallbladder surgery increases. This project will develop a process to affect the entire surface of the gallbladder ("ablation"), inducing a healing response that will defunctionalize the gallbladder and obviate the need to remove it. This is the first technology designed to conduct this process within a tube via a minimally invasive approach. Ultimately, this technology could be adapted to create more effective devices for other high surface area tissue targets.The proposed project is a significant improvement over current state-of-practice ablation devices due to its ability to deliver high-surface area ablation within a closed lumen or organ, such as the gallbladder. Existing conductive devices are designed for targeted ablation of discrete lesions rather than therapeutic delivery to large tissue targets, such as the gallbladder. The aim of this project is to develop a new process using open lumen instillation of cryogen to achieve high surface area cryoablation of tissues. This raises several unique engineering challenges, including the design of a delivery mechanism for the uniform distribution of cryogen across a closed lumen and development of a pressure management system to properly evacuate the cryogen gas and prevent an increase in intraluminal pressure. Initial optimization of the cryogen distribution and pressure management system will be conducted using a benchtop thermal load model of the gallbladder to approximate the in vivo thermodynamics. Optimized designs will then be tested in acute and chronic animal models to demonstrate the safety and efficacy of open lumen instillation of cryogen for high surface area intraluminal cryoablation of the gallbladder.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will be the development of the first minimally invasive cryoablation solution to treat high-risk patients with gallbladder disease. The current gold standard for treating gallbladder disease is surgical removal of the gallbladder. While this procedure works well for healthy patients, the use of general anesthesia has been shown to increase complications in elderly patients with underlying chronic medical conditions, leading to a $675 million cost to the US healthcare system each year. Furthermore, patients too sick for surgery have no definitive treatment options, underscoring the need for a safer alternative. Phase I efforts demonstrated the ability to safely deliver cryoablation energy via a minimally invasive catheter system to chronically defunctionalize porcine gallbladders without removal. Phase II efforts will focus on product development of the cryoablation system and optimization of clinical delivery parameters. The goal of the technology is to allow clinicians to provide their patients with the benefits of surgery, without the risk.This Small Business Innovation Research (SBIR) Phase II project proposes to continue the development of a minimally invasive cryoablation system capable of safely and effectively targeting the gallbladder. Initial testing of the cryoablation system has demonstrated the ability to uniformly generate lethal cryoablation temperatures (<-20?) across the gallbladder lumen, leading to durable gallbladder scarring and defunctionalization in porcine animals up to 60 days post-procedure. Key technical objectives of this project are to develop the industrial design of the introducer, cryoablation catheter, and control system for improved clinical usability and manufacturability, to further test and characterize clinical delivery parameters to inform treatment planning, to improve sensor reliability and control system response time to optimize safety profile, and to validate the integrated system in vivo to demonstrate system performance with optimized dosing parameters. The system will be evaluated in an advanced benchtop model gallbladder under a thermal load, ex vivo gallbladder tissues, and an in vivo chronic animal model to optimize and validate the cryoablation catheter and integrated control system. The anticipated result of this project is a clinically viable gallbladder cryoablation system with established clinical delivery parameters and dosing guidelines.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.