Wirelessly-operated Implantable MEMS Micropumps for Drug Infusion in Mice

用于小鼠药物输注的无线植入式 MEMS 微型泵

• 批准号: 8534210
• 负责人: Ellis Meng
• 金额: $ 17.79万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-20 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8534210
• 关键词: Address; Aggressive behavior; Animal Behavior; Animals; Behavior; Biocompatible; Biocompatible Materials; Bolus Infusion; Catheters; Chemicals; Chronic; Clinical; Computer software; Development; Devices; Disease; Dose; Drug Controls; Drug Delivery Systems; Engineering; Environment; Environmental Risk Factor; External Infusion Pumps; Goals; Hand; Hormones; Human; Implant; Implantable Infusion Pumps; Implantable Pump; Individual; Infusion Pumps; Infusion procedures; Injection of therapeutic agent; Intravenous; Knock-out; Knockout Mice; Laboratory Animals; Laboratory Research; Link; Manuals; Mechanics; Medicine; Methods; Microfabrication; Miniaturization; Modeling; Morphologic artifacts; Motor; Movement; Mus; Needles; Neurosciences; Operative Surgical Procedures; Oral; Oral Administration; Organ; Oryctolagus cuniculus; Osmosis; Outcome; Outcome Study; Outcomes Research; Performance; Pharmaceutical Preparations; Pharmacology; Physiological; Physiology; Play; Procedures; Pump; Rattus; Regimen; Research; Research Personnel; Rodent; Role; Route; Simulate; Stress; System; Techniques; Technology; Telemetry; Testing; Transgenic Organisms; Weight; Wireless Technology; base; cost; drug development; experience; graphical user interface; human disease; implantable device; implantation; improved; in vivo; intraperitoneal; minimally invasive; mouse model; new technology; novel; operation; preclinical study; research study; response; tool

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.

描述（由申请人提供）：小鼠，尤其是人类疾病的转基因和敲除模型，已用于实验室研究和临床前研究，并对包括神经科学，医学和药理学在内的许多领域产生了深远的影响。但是，在小鼠中，慢性药物管理的实际工具很少。传统方法最频繁地利用涉及限制和密集处理动物的口服，静脉和腹膜内路线。动物的手动处理仅提供间歇性给药，并且已知会引起压力和其他重要的生理影响，从而改变了实验结果。外部输注泵或可植入的渗透泵可以连续给药。外部泵需要限制自然运动并重塑正常行为的导管系tether。渗透泵具有固定的药物有效载荷，无法补充渗透泵，从而限制了它们在慢性研究中的使用。目前没有可植入的泵 无线操作，可以实现任何所需的药物释放概况。这些能力的结合将为小鼠和其他较小动物的慢性研究提供一种新工具，而无需处理。 为了实现这一目标，我们提出了一个适合小鼠长期药物给药的无线且可再填充的植入式输液泵。该泵平台基于我们先前的经验，为大鼠和兔子等大型动物开发可植入的泵。在这里，我们将解决工程挑战，以使实现鼠标泵所需的规模减少十倍。通过使用微加工技术来减小泵组件的大小而不会损害其电气或机械性能（特定的AIM 1）来启用这一点。泵将与无线遥测和软件图形用户界面组装并集成，该泵可以使用户启动的泵的远程激活在标准鼠标笼中的任何位置（特定的AIM 2）。我们将证明对药物给药的精确控制，以便通过使用WIIP将化合物传递到模拟的生物材料中，可以实现任何所需的药物释放概况（特定目标3）。 WIIP将在长期实验中以无手，无针和无链球的方式在体内对药物概况的前所未有的控制。这样一来，WIIP将在更自然的环境中进行研究，对没有压力相关的伪影的药物反应的更可靠的评估，并允许与人造动物/人类相互作用进行全天候的药物输送。 WIIP为实验室研究和临床前研究提供了一种变革性的新工具，可用于广泛的生物医学应用。