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)第二阶段项目将微电子技术的精确度与低功率微流体相结合，实现了一种专为啮齿动物药物输送应用量身定做的全植入式微泵。目前，给药主要以手工操作和针头注射为主，劳动强度大，容易产生压力等问题。效果，并且仅限于简单的药物释放概况。需要先进的动物给药能力，使新的复杂剂量分布成为可能，为慢性研究提供自动化，并提高科学有效性。技术挑战包括低功率感应动力泵执行器的开发、十倍泵的小型化以及大量植入式泵的无线控制。研究目标是(1)优化泵的性能和可用性(2)扩大保持架尺寸的兼容性和连接性(3)优化软件可用性(4)优化系统设计和建立放大的质量保证过程以及(5)进行体内验证研究。遥控植入式输液泵系统的成功演示将使新的剂量方案成为可能，为急慢性研究的更具重复性的结果提供精确的时间控制剂量，并使原本不可能实现的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/发现进程。目前，每10,000个候选药物中只有一个成功获得FDA的批准，相当数量的候选药物因药物管理不当而失败或被放弃。通过该第二阶段项目支持的全自动、无线控制的药物剂量技术，可以在药物开发过程的早期快速准确地评估疗效、安全性和毒性。该项目的目标市场是国际实验动物市场，预计2012年市场规模为34亿美元。动物模型被应用于整个药物开发流水线，尤其是啮齿动物对候选药物靶标的验证、筛选和优化至关重要。这一努力包括几项重要的率先上市的能力，例如在自由移动、无系绳的小鼠上的慢性给药能力，以及通过自动化对多种新药进行高通量评估。药物的控制输送，包括新兴的生物制品、siRNA、多肽和小分子，是包括神经科学、药理学、毒理学和生理学在内的许多临床和临床前研究应用的重要能力。更重要的是，该项目将使药物研究能够以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.