SBIR Phase II: Wirelessly Operated Implantable Micropump for On-demand Drug Administration in Laboratory Animals

这个小型企业创新研究（SBIR）二期项目将微技术的精度与低功率微流体结合起来，实现了一种专门为啮齿类动物的药物输送应用量身定制的完全可植入的微泵。目前，给药主要是通过人工操作和针头注射进行的，这是劳动密集型的，会引起压力和其他“白大褂”。影响，并仅限于简单的药物释放概况。需要先进的动物给药能力，以实现新的复杂给药谱，为慢性研究提供自动化，并提高科学有效性。技术挑战包括开发低功率电感驱动的泵致动器，十倍泵小型化和大量植入泵的无线控制。研究目标是：(1)优化泵的性能和可用性(2)扩展笼型尺寸的兼容性和连接性(3)优化软件可用性(4)优化系统设计并建立用于扩大规模的质量保证流程(5)进行体内验证研究。远程控制植入式输液泵系统的成功演示将启用新的给药方案，为急性和慢性研究提供更可重复的精确的临时控制给药，并使药物治疗的新方法成为可能。该项目更广泛的影响/商业潜力在于独特地改善科学成果和促进药物开发/发现过程。目前，只有万分之一的候选药物成功获得FDA批准，大量候选药物由于药物管理不足而失败或被丢弃。通过该二期项目支持的全自动、无线控制给药技术，提高了在药物开发过程早期对疗效、安全性和毒性的快速、准确评估。该项目的目标是国际实验动物市场，预计2012年将达到34亿美元。动物模型在整个药物开发管道中使用，特别是啮齿动物对候选药物靶点验证，筛选和优化至关重要。这项工作包括几个重要的首次进入市场的能力，如自由移动、无系绳小鼠的慢性给药能力，以及通过自动化对多种新药进行高通量评估。药物的控制递送，包括新兴生物制剂、siRNA、多肽和小分子，是众多临床和临床前研究应用的重要能力，包括神经科学、药理学、毒理学和生理学。更重要的是，该项目将使药物研究能够以一种促进和加强候选疗法从动物到人类的转化的方式进行。

This Small Business Innovation Research (SBIR) Phase II project couples the precision of microtechnology with low-power microfluidics to realize a fully-implantable micropump specifically tailored for drug delivery applications in rodents. Currently, drug administration is predominantly conducted by manual handling and needle injection which is labor-intensive, induces stress and other ?white-coat? effects and is limited to simple drug release profiles. There is a need for advanced drug administration capability in animals that enables new complex dosing profiles, provides automation for chronic studies, and improves scientific validity. Technical challenges include the development of a low-power inductively-powered pump actuator, ten-fold pump miniaturization and wireless control of a large number of implanted pumps. The research objectives are (1) to optimize pump performance and usability (2) to extend cage size compatibility and connectivity (3) to optimize software usability (4) to optimize system design and establish quality assurance processes for scale-up and (5) to conduct an in-vivo validation study. Successful demonstration of the remotely-controlled implantable infusion pump system will enable new dosing schemes, provide precise temporally controlled dosing for more reproducible results from acute and chronic studies, and enable new approaches to drug therapy that would not otherwise be possible. The broader impact/commercial potential of this project lies in uniquely improving scientific outcomes and facilitating the drug development/discovery process. Currently, only one in 10,000 drug candidates successfully attain FDA approval with a significant number of candidates failing or discarded due to inadequate drug administration. Rapid and accurate evaluation of efficacy, safety and toxicity early in the drug development process is improved through the fully automated, wirelessly-controlled drug dosing technology supported by this Phase II project. This project targets the international laboratory animal market estimated at $3.4B in 2012. Animal models are employed throughout the drug development pipeline and in particular, rodents are critical to drug candidate target validation, screening, and optimization. Included in this effort are several significant first-to-market capabilities such as chronic dosing capability in freely-moving, tether-free mice and high-throughput evaluation of multiple new drugs through automation. The controlled delivery of agents, including emerging biologics, siRNA, peptides, and small molecules, is an important capability in a multitude of clinical and preclinical research applications including neuroscience, pharmacology, toxicology, and physiology. More importantly, this project will enable drug studies that to be performed in a manner that will facilitate and enhance the translation of candidate therapies from animal to human.