SBIR Phase I: Improved Skeletal Visualization Technology for Developmental and Reproductive Toxicology (DART) Studies

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力将是开发技术，以改善发育和生殖毒理学（DART）研究的骨骼可视化。美国每年花费超过40亿美元用于新药、化妆品、杀虫剂和工业化学品的毒理学研究。测试时间或成本的任何减少都可以为这些行业带来巨大的利益，使更安全的化学产品更快地以更低的成本进入市场。使用这项技术将减少研究人员的时间和完成常规研究所需的实验室动物数量，从而更快，更有效地对新化学品进行安全筛选。其目的是使合同研究组织（CRO）每年能够进行30%以上的研究，同时降低成本。这些研究是必要的，以确保进入市场的化学品是安全的。 进行这些研究的CRO目前在满足客户需求方面面临着非常大的挑战。 由于欧盟最近的REACH立法，对DART研究的需求迅速上升，积压导致消费者获得化学品和拯救生命的治疗药物的速度更慢。该SBIR第一阶段项目提出开发一种用于啮齿动物骨骼结构可视化的透明剂。目的是证明所提出的技术可以快速清除组织而不会对标本造成损伤。 目前使用的方法，透音化，主要问题是它的倾向，破坏标本超出可用性，并需要时间来完成这一过程。 目前，最长的步骤是处理动物以评估其骨骼，这需要14-21天的时间，其中软组织用强碱消化，骨骼染色，以便更容易观察。所提出的技术能够使软组织透明，使得骨骼可以在2-6天内容易地可视化。通过该项目，该技术将被优化以取代DART研究中骨骼可视化的当前方法，然后在并行研究中进行比较，以确定是否在不损坏标本的情况下达到相同的终点，同时将总体研究时间减少30%以上并降低成本。该项目将直接导致一种技术，可以出售给CRO，以取代他们目前的骨骼可视化技术，使他们能够大幅提高研究吞吐量和质量。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be to develop technology to improve skeletal visualization for developmental and reproductive toxicology (DART) studies. Every year over $4 billion is spent in the US on toxicology studies for new pharmaceuticals, cosmetics, pesticides, and industrial chemicals. Any reduction in testing times or costs could create significant benefits to these industries by bringing safer chemical products to market more quickly and at lower costs. Using this technology would reduce both researcher time and the number of laboratory animals needed to complete common studies, leading to faster and more efficient safety screening for new chemicals. The aim is to enable contract research organizations (CRO's) to conduct 30% more studies per year while reducing costs. These studies are required to ensure that chemicals that make it into the market place are safe. CRO's that conduct these studies currently have a very challenging time meeting customer demand. The demand for DART studies has risen quickly due to the recent REACH legislation in the European Union, and the back-log has resulted in chemicals and life-saving therapeutics being available to consumers more slowly. This SBIR Phase I project proposes to develop a clearing agent for the visualization of bone structures in rodents. The goal is to demonstrate the proposed technology can rapidly clear tissue without causing damage to the specimens. The major problem with the currently used method, diaphonization, is its tendency to destroy specimens beyond usability, and the time required to complete the process. Currently, the longest step is processing the animals to evaluate their skeletons, which is conducted using a process requiring 14-21 days where the soft tissue is digested with a strong base and the bones are stained so they can be more easily visualized. The proposed technology is able to render the soft tissue transparent so that the bones can be easily visualized in 2-6 days. Through this project the technology will be optimized for replacing the current approach to skeletal visualization in DART studies, and then compared in a side-by-side study to determine if the same end point is reached without damage to the specimens while reducing overall study time by over 30% and reducing costs. This project will lead directly to a technology that can be sold to CRO's to replace their current skeletal visualization technology with an approach that enables them to drastically increase study throughput and quality.