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

这一小型企业创新研究(SBIR)项目的更广泛影响/商业潜力将是开发技术，以改进发育和生殖毒理学(DART)研究的骨骼可视化。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以更快的速度和更低的成本将更安全的化学产品推向市场，从而为这些行业带来巨大的好处。使用这项技术将减少研究人员的时间和完成常见研究所需的实验室动物数量，从而导致对新化学品进行更快、更有效的安全筛选。其目的是使合同研究机构(CRO)在降低成本的同时，每年多进行30%的研究。这些研究是必需的，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具有挑战性的时间。由于欧盟最近的REACH立法，对DART研究的需求迅速上升，积压导致化学物质和挽救生命的疗法向消费者提供的速度变慢。这项SBIR第一阶段项目建议开发一种用于啮齿类动物骨骼结构可视化的清洗剂。其目的是证明拟议的技术可以快速清除组织，而不会对标本造成损害。目前使用的重发音方法的主要问题是，它往往会破坏样品，使其无法使用，而且完成这一过程需要时间。目前，最长的步骤是处理动物以评估它们的骨骼，这一过程需要14-21天，软组织用强大的碱消化，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变得透明，因此可以在2-6天内轻松地显示骨骼。通过该项目，该技术将在DART研究中取代目前的骨骼可视化方法进行优化，然后在并排研究中进行比较，以确定是否在不损坏样本的情况下达到相同的终点，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可以出售给CRO的技术，用一种使他们能够大幅提高研究吞吐量和质量的方法来取代他们目前的骨骼可视化技术。

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.