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

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力是开发一种具有成本效益，环境和经济合理的鲎变形细胞溶解物（LAL）生产设施，该设施基于有限数量的马蹄蟹（HSC），使用影响最小的新型出血程序。 目标是满足每年超过10亿美元的LAL市场和成品试剂盒市场的需求。该项目的成功还有望通过确保生物医学和制药业符合现行标准，使马蹄蟹总数少于每年因现行做法死亡的数量。本项目中开发的HSC出血新方法还将实现重复控制出血，同时保持动物活力和邻近社区的最佳条件。假设优化的，可扩展的HSC出血操作最终可以扩大目前的供应，可以开发创新的应用。例如，败血症的早期检测可以帮助避免每年在美国的直接护理中花费约300亿美元，尽管随着医院获得性败血症的革兰氏阴性筛查工具的发展，有可能挽救无数生命。总体目标是证明设计用于促进常规出血而不影响HSC完整性和健康的植入式和外科级器械的概念验证。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，同时避免将其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配对的商业机会和可行性，以系统地监测HSC的健康状况。该SBIR I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，该技术自19世纪末以来一直没有发生重大变化。鉴于供应链中的LAL过剩，该提议的方法还有望大规模提高产品质量和可追溯性，并最终提高生产LAL试剂盒的公司的底线。该奖项反映了NSF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.