Wirelessly-operated Implantable MEMS Micropumps for Drug Infusion in Mice

描述（由申请人提供）：小鼠，特别是人类疾病的转基因和基因敲除模型，已被用于实验室研究和临床前研究，并对许多领域产生了深远的影响，包括神经科学、医学和药理学。然而，很少有实用的工具存在于小鼠慢性给药。传统方法最常用的是口服、静脉注射和腹腔注射途径，包括限制和密集处理动物。人工处理动物只能提供间歇性给药，并且已知会引起应激和其他可能改变实验结果的重大生理影响。连续给药是可能的外部输液泵或植入式渗透泵。外部泵需要导管系带，限制自然运动和重塑正常行为。渗透泵具有固定的药物载荷，不能重新填充，这限制了它们在慢性研究中的使用。目前还没有植入式泵

DESCRIPTION (provided by applicant): Mice, especially transgenic and knockout models of human diseases, have been used in laboratory research and preclinical studies and have had profound impact on many fields, including neuroscience, medicine, and pharmacology. However, few practical tools exist for chronic drug administration in mice. Traditional methods most frequently utilize the oral, intravenous, and intraperitoneal routes that involve restraining and intensive handling of animals. Manual handling of animals provides only intermittent dosing and is known to induce stress and other significant physiological impacts that may alter experimental outcomes. Continuous dosing is possible with external infusion pumps or implantable osmotic pumps. External pumps require catheter tethers that limit natural movement and reshapes normal behavior. Osmotic pumps have a fixed drug payload and cannot be refilled which limits their use in chronic studies. No implantable pump is currently available that is wirelessly-operated and can achieve any desired drug release profile. The combination of these capabilities will provide a new tool for precise drug administration in chronic studies in mice and other smaller animals without the need for handling. To achieve this goal, we propose a wirelessly-operated and refillable implantable infusion pump that is suitable for chronic drug administration in mice. This pump platform is based on our prior experience developing implantable pumps for larger animals such as rats and rabbits. Here, we will address the engineering challenges to enable a tenfold reduction in scale required to realize a mouse pump. This is enabled by using microfabrication techniques to reduce the size of pump components without compromising their electrical or mechanical performance (Specific Aim 1). Pumps will be assembled and integrated with wireless telemetry and a software graphical user interface that enables user-initiated remote activation of the pump anywhere within a standard mouse cage (Specific Aim 2). We will demonstrate precise control of drug administration such that any desired drug release profile can be achieved by using WIIP to deliver compounds into simulated biological materials (Specific Aim 3). WIIP will enable unprecedented control of drug profiles in vivo in long term experiments in a hands-free, needle-free, and tether-free manner. In doing so, WIIP will enable studies in more naturalistic environments, more reliable assessment of drug responses without stress-related artifacts, and allow around-the-clock drug delivery with artificial animal/human interactions. WIIP provides a transformative new tool for both laboratory research and preclinical studies that is applicable to a broad range of biomedical applications.