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，以改善骨骼可视化的发育和生殖毒理学（DART）研究。美国每年在新药、化妆品、杀虫剂和工业化学品的毒理学研究上花费超过40亿美元。任何测试时间或成本的减少都可以通过更快、更低成本地将更安全的化学产品推向市场，为这些行业创造巨大的利益。使用这种技术将减少研究人员完成普通研究所需的时间和实验动物的数量，从而更快、更有效地对新化学品进行安全筛选。其目的是在降低成本的同时，使合同研究组织（CRO）每年多进行30%的研究。这些研究是为了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非常具有挑战性。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救生疗法的速度更慢。本SBIR一期项目拟开发一种用于啮齿类动物骨结构可视化的清除剂。目标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害。目前使用的失音化方法的主要问题是其破坏标本的趋势超出了可用性，并且需要完成该过程的时间。目前，最长的步骤是对动物进行处理，以评估它们的骨骼，这需要14-21天的时间，在这个过程中，软组织被一个坚固的基础消化，骨骼被染色，这样它们就更容易被观察到。所提出的技术能够使软组织透明，因此骨骼可以在2-6天内很容易地可视化。通过该项目，该技术将被优化，以取代目前DART研究中的骨骼可视化方法，然后在并排研究中进行比较，以确定是否达到相同的终点而不损坏标本，同时将整体研究时间缩短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的吞吐量和质量。

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.