A non-invasive high-throughput sleep stage analysis system

描述(申请人提供)：睡眠质量随年龄的下降是一个有据可查的现象。虽然关于这种下降的特征我们知道得很多，但对其生理或遗传基础的了解却非常少。啮齿动物(小鼠+大鼠)与年龄相关的睡眠变化与人类的睡眠变化非常相似，因此这些动物模型经常被用来研究衰老过程。然而，目前测量啮齿动物睡眠所需的最先进技术需要外科手术植入脑电和肌电图仪(EMG)探头。这一过程的缺点包括需要进行侵入性且耗时的动物手术，同时需要较长的恢复期。时间部分极其缓慢，因为动物必须从手术中恢复，并适应记录室和系绳，然后才能评估正常睡眠。此外，植入螺丝钉的生物污垢和慢性种植体的腐烂会随着时间的推移改变信号质量，并将长期记录限制在连续几个月内。人工费用包括需要聘请一名专业技术人员来操作设备、进行手术和评估睡眠数据。为了克服这些困难，我们计划使用加速视频硬件、3-D视频监控和深红色网格(啮齿动物看不见)来测量睡眠状态。在这项应用的第一阶段，Pinnacle Technology Inc.和宾夕法尼亚大学睡眠和呼吸神经生物学中心将创建一个工作原型(软件、电子和硬件)，用于非侵入性检测啮齿动物的睡眠状态。具体地说，该系统的目标是成为第一个使用非手术、非侵入性技术记录和自动分析啮齿动物的觉醒、NREM和REM睡眠的商业设备。这种设计的一个独特的好处是，它将能够在整个生命周期内连续记录同一动物的睡眠-觉醒结构。该系统一旦得到验证，就可以很容易地作为大规模筛查工具来快速筛查数百只动物。大型制药公司已经在寻求这种设备的商业应用，因为他们正在探索用于靶向治疗的新的潜在基因产品。 与公共健康相关：据估计，每年至少有4000万美国人患有慢性、长期的睡眠障碍，另有2000万人偶尔出现睡眠问题。随着年龄的增长，睡眠障碍变得更加普遍；超过50%的比年长的人患有睡眠障碍。从经济上讲，睡眠不佳每年造成的医疗成本估计高达160亿美元，而生产力下降和其他因素造成的间接成本众所周知要高得多。

DESCRIPTION (provided by applicant): Degeneration of sleep quality with age is a well-documented phenomenon. While much is known regarding the characterization of this decline, remarkably little of the physiology or genetic underpinnings are understood. Age-related sleep changes in rodents (mice + rats) are remarkably similar to those seen in human populations and as such these animal models are frequently used to study the aging process. However, the current state-of-the-art technology necessary for measuring sleep in rodents requires surgical implantation of EEG and electromyograph (EMG) probes. Drawbacks to this process include the need for an invasive and time-consuming animal surgery paired with a prolonged recovery period. The time component is extremely slow as the animal must recover from surgery and acclimate to the recording chamber and tether before normal sleep can be evaluated. Additionally, biofouling of the implanted screws and decay of the chronic implant alters signal quality over time and restricts long-term recordings to only a few continuous months. Labor expenses include the need to hire an expert technician to run the equipment, undertake surgery and evaluate sleep data. To overcome these difficulties we plan to use accelerated video hardware, 3-D video monitoring and a deep red grid (invisible to the rodent) to measure sleep state. In Phase I of this application, Pinnacle Technology Inc and the University of Pennsylvania Center for Sleep and Respiratory Neurobiology will create a working prototype (software, electronics, and hardware) for non-invasive detection of sleep state in rodents. Specifically, this system aims to be the first commercial device designed to record and automatically analyze wake, NREM and REM sleep in rodents using non-surgical, non-invasive techniques. A unique benefit to this design is that it will be capable of continuously recording sleep-wake architecture from the same animal across the lifespan. The system, once validated, can easily be used as a large-scale screening tool to rapidly screen hundreds of animals. Commercial applications of such a device are already being sought by major pharmaceutical companies as they explore new potential gene products for targeted therapy. PUBLIC HEALTH RELEVANCE: It is estimated that at least 40 million Americans suffer each year from chronic, long-term sleep disorders while an additional 20 million experience occasional sleeping problems. As people age, sleeping disorder are more prevalent; more than 50 percent of people older than 64 have a sleep disorder. Economically, poor sleep accounts for an estimated $16 billion in medical costs each year and the indirect costs of lost productivity and other factors are known to be much higher.