SBIR Phase I: A Novel Horseshoe Crab Device and Approach for a Sustainable Endotoxin Testing Resource

这项小型企业创新研究（SBIR）项目的更广泛影响/商业潜力是开发一种成本效益高、环保且经济合理的鲎试剂（LAL）生产设备，该设备基于有限数量的马蹄蟹（HSC），使用影响最小的新型出血程序。目标是满足估计1.14亿美元的LAL市场和每年超过10亿美元的成品套件市场的需求。该项目的成功还有望超过目前的标准，确保生物医学和制药生产符合要求，减少马蹄蟹的总数，而不是每年因目前的做法而死亡的马蹄蟹数量。在该项目中开发的HSC出血新方法也将实现重复，控制出血，同时为动物活力和邻近社区保持最佳条件。假设优化的、可扩展的HSC出血手术最终可以扩大现有的供应，创新的应用可以被开发出来。例如，尽管医院获得性败血症革兰氏阴性筛查工具的发展有可能挽救无数生命，但在美国，败血症的早期检测每年可帮助避免约300亿美元的直接护理费用。该SBIR一期项目提出开发一种可替代的马蹄蟹（hsc）出血方法，用于鲎细胞裂解物（LAL）的收获。总体目标是展示一种可植入的概念验证，手术级设备设计用于促进常规出血，而不会损害HSC的完整性和健康。这将通过对HSC出血结果的系统研究来实现，以调查这种设备是否能够满足传统方法的无菌性和质量标准，同时避免不必要的运输到昂贵的内陆出血设施。此外，将研究该设备与基于栖息地的封闭系统相结合的商业机会和可行性，以系统地监测HSC的健康状况。这个SBIR一期项目将是第一个研究造血干细胞出血的替代方法的项目，这项技术自19世纪后期以来没有发生过重大变化。在规模上，所提议的方法也有望提高产品质量和可追溯性，并最终提高生产LAL套件的公司的底线，因为供应链中有LAL的盈余。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is the development of a cost-effective, environmental and economically sound Limulus amebocyte lysate (LAL) production facility based on a finite number of horseshoe crabs (HSC) using minimally impactful and novel bleeding procedures. The goal is to address the demands of an estimated $114 million LAL market and finished kit market in excess of $1 billion per annum. Success of this project also anticipates exceeding current standards by ensuring biomedical and pharmaceutical manufacturing compliance with fewer total horseshoe crabs than the number that die annually from current practices. New approaches to HSC bleeding developed in this project would also enable repeated, controlled bleeding while maintaining optimal conditions for animal vitality and for the adjacent communities. Assuming optimized, scalable HSC bleeding operations could eventually expand current supplies, innovative applications could be developed. For example, early detection of sepsis could help avert some $30 billion in direct care every year in the US, notwithstanding the potential to save countless lives with development of gram-negative screening tools for hospital acquired septicemia.This SBIR Phase I project proposes to develop an alternative method of bleeding horseshoe crabs (HSCs) for Limulus amebocyte lysate (LAL) harvest. The overarching objective to demonstrate the proof-of-concept of an implantable, and surgical-grade device engineered to facilitate routine bleeding, without compromising the integrity and well-being of the HSC. This will be achieved via a systematic study of HSC bleeding outcomes to investigate whether such a device can meet the sterility and quality standards of traditional approaches, while obviating the need for extraneous transport to expensive, inland bleeding facilities. Furthermore, the commercial opportunity and feasibility of the device paired with a habitat-based, enclosed system to systematically monitor HSC wellbeing will be investigated. This SBIR Phase I project would be the first to investigate an alternative approach to bleeding HSCs, a technique that has not changed significantly since the late 1800's. At scale, the proposed approach would also be expected to improve product quality and traceability, and ultimately the bottom line of companies producing LAL kits, given a surplus of LAL in the supply chain.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.